Skip to content
2000
image of Cancer Stem Cell-targeted Antibody-drug Conjugates for Cancer Immunotherapy
file format pdf download PDF

Abstract

Cancer stem cells (CSCs) participate in cancer initiation, metastasis, and therapy tolerance, presenting a formidable challenge in cancer treatment. Antibody-drug conjugates (ADCs) have been established as a potential strategy for selectively targeting and eradicating CSCs, thereby overcoming resistance mechanisms and preventing tumor recurrence. ADCs integrate a monoclonal antibody specific to CSC surface markers, such as CD44, CD133, EpCAM, and ALDH1, with a potent cytotoxic payload linked by a stable chemical linker. Upon antigen binding, ADCs undergo receptor-mediated internalization, leading to intracellular payload release and CSC apoptosis. Recent advances in ADC technology have enhanced selectivity and efficacy while minimizing off-target toxicity. Preclinical studies demonstrate that CSC-targeted ADCs, including CD133- and CD44-directed therapies, effectively deplete CSC populations in glioblastoma, breast, colorectal, and lung cancers. EpCAM-targeted ADCs have also shown efficacy in epithelial tumors with potential synergy in combination immunotherapies. Moreover, emerging approaches, such as bispecific antibodies and optimized linker chemistry, further refine CSC-targeted ADCs for clinical applications. Despite these advancements, challenges remain, including CSC heterogeneity, immune evasion, and limitations in biomarker specificity. Addressing these hurdles requires continued innovation in ADC engineering, novel payloads, and combinatory strategies with immune checkpoint inhibitors or CAR-T cell therapies. While clinical evaluations are still in the early phases, preliminary trials underscore the potential of CSC-targeted ADCs in revolutionizing precision oncology. This review explores the mechanisms, recent developments, and prospects of CSC-targeted ADCs, highlighting their transformative potential in cancer immunotherapy.

© 2025 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673393449250818052754
2025-09-11
2025-11-06

  • From This Site

    /content/journals/cmc/10.2174/0109298673393449250818052754
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/cmc/10.2174/0109298673393449250818052754/BMS-CMC-2025-HT146-6192-6.html?itemId=/content/journals/cmc/10.2174/0109298673393449250818052754&mimeType=html&fmt=ahah

References

  1. Zhou H. Tan L. Liu B. Guan X.Y. Cancer stem cells: Recent insights and therapies. Biochem. Pharmacol. 2023 209 115441 10.1016/j.bcp.2023.115441 36720355
    [Google Scholar]
  2. Batlle E. Clevers H. Cancer stem cells revisited. Nat. Med. 2017 23 10 1124 1134 10.1038/nm.4409 28985214
    [Google Scholar]
  3. Takebe N. Miele L. Harris P.J. Jeong W. Bando H. Kahn M. Yang S.X. Ivy S.P. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: Clinical update. Nat. Rev. Clin. Oncol. 2015 12 8 445 464 10.1038/nrclinonc.2015.61 25850553
    [Google Scholar]
  4. Hussain M.S. Tyagi S. Khatri H. Singh S. Stem cell therapy for myocardial infarction: A mini-review. Asian J. Pharm. Res. Dev. 2022 10 2 122 124 10.22270/ajprd.v10i2.1155
    [Google Scholar]
  5. O’Connor M.L. Xiang D. Shigdar S. Macdonald J. Li Y. Wang T. Pu C. Wang Z. Qiao L. Duan W. Cancer stem cells: A contentious hypothesis now moving forward. Cancer Lett. 2014 344 2 180 187 10.1016/j.canlet.2013.11.012 24333726
    [Google Scholar]
  6. Ahad Mir P.R.I.N.C.E. Hussain M.S. Ahmad Khanday M. Mohi-ud-din R. Pottoo F.H. Hasssan Mir R. Immunomodulatory roles of mesenchymal stem cell-derived extracellular vesicles: A promising therapeutic approach for autoimmune diseases. Curr. Stem Cell Res. Ther. 2024 20 10.2174/011574888X341781241216044130 39757602
    [Google Scholar]
  7. Li S. Ling S. Wang D. Wang X. Hao F. Yin L. Yuan Z. Liu L. Zhang L. Li Y. Chen Y. Luo L. Dai Y. Zhang L. Chen L. Deng D. Tang W. Zhang S. Wang S. Cai Y. Modified lentiviral globin gene therapy for pediatric β 0 /β 0 transfusion-dependent β-thalassemia: A single-center, single-arm pilot trial. Cell Stem Cell 2024 31 7 961 973.e8 10.1016/j.stem.2024.04.021 38759653
    [Google Scholar]
  8. Plaks V. Kong N. Werb Z. The cancer stem cell niche: How essential is the niche in regulating stemness of tumor cells? Cell Stem Cell 2015 16 3 225 238 10.1016/j.stem.2015.02.015 25748930
    [Google Scholar]
  9. Tanabe S. Quader S. Cabral H. Ono R. Interplay of EMT and CSC in cancer and the potential therapeutic strategies. Front. Pharmacol. 2020 11 904 10.3389/fphar.2020.00904 32625096
    [Google Scholar]
  10. Hussain M.S. Mujwar S. Babu M.A. Goyal K. Chellappan D.K. Negi P. Singh T.G. Ali H. Singh S.K. Dua K. Gupta G. Balaraman A.K. Pharmacological, computational, and mechanistic insights into triptolide’s role in targeting drug-resistant cancers. Naunyn Schmiedebergs Arch. Pharmacol. 2025 10.1007/s00210‑025‑03809‑5
    [Google Scholar]
  11. Romaniuk-Drapała A. Totoń E. Taube M. Idzik M. Rubiś B. Lisiak N. Breast cancer stem cells and tumor heterogeneity: Characteristics and therapeutic strategies. Cancers 2024 16 13 2481 10.3390/cancers16132481 39001543
    [Google Scholar]
  12. Yang H. Li Q. Chen X. Weng M. Huang Y. Chen Q. Liu X. Huang H. Feng Y. Zhou H. Zhang M. Pei W. Li X. Fu Q. Zhu L. Wang Y. Kong X. Lv K. Zhang Y. Sun Y. Ma M. Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer. Nat. Commun. 2024 15 1 4296 10.1038/s41467‑024‑48307‑z 38769295
    [Google Scholar]
  13. Moitra K. Overcoming multidrug resistance in cancer stem cells. BioMed Res. Int. 2015 2015 1 8 10.1155/2015/635745 26649310
    [Google Scholar]
  14. Bao S. Wu Q. McLendon R.E. Hao Y. Shi Q. Hjelmeland A.B. Dewhirst M.W. Bigner D.D. Rich J.N. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006 444 7120 756 760 10.1038/nature05236 17051156
    [Google Scholar]
  15. Hussain M.S. Afzal O. Gupta G. Altamimi A.S.A. Almalki W.H. Alzarea S.I. Kazmi I. Fuloria N.K. Sekar M. Meenakshi D.U. Thangavelu L. Sharma A. Long non-coding RNAs in lung cancer: Unraveling the molecular modulators of MAPK signaling. Pathol. Res. Pract. 2023 249 154738 10.1016/j.prp.2023.154738 37595448
    [Google Scholar]
  16. Medema J.P. Cancer stem cells: The challenges ahead. Nat. Cell Biol. 2013 15 4 338 344 10.1038/ncb2717 23548926
    [Google Scholar]
  17. Tsuchiya H. Shiota G. Immune evasion by cancer stem cells. Regen. Ther. 2021 17 20 33 10.1016/j.reth.2021.02.006 33778133
    [Google Scholar]
  18. Chen Y. Deng Y. Li Y. Qin Y. Zhou Z. Yang H. Sun Y. Oxygen-independent radiodynamic therapy: Radiation-boosted chemodynamics for reprogramming the tumor immune environment and enhancing antitumor immune response. ACS Appl. Mater. Interfaces 2024 16 17 21546 21556 10.1021/acsami.4c00793 38626342
    [Google Scholar]
  19. Wu B. Shi X. Jiang M. Liu H. Cross-talk between cancer stem cells and immune cells: Potential therapeutic targets in the tumor immune microenvironment. Mol. Cancer 2023 22 1 38 10.1186/s12943‑023‑01748‑4 36810098
    [Google Scholar]
  20. Yang Z. Liu X. Xu H. Teschendorff A.E. Xu L. Li J. Fu M. Liu J. Zhou H. Wang Y. Zhang L. He Y. Lv K. Yang H. Integrative analysis of genomic and epigenomic regulation reveals miRNA mediated tumor heterogeneity and immune evasion in lower grade glioma. Commun. Biol. 2024 7 1 824 10.1038/s42003‑024‑06488‑9 38971948
    [Google Scholar]
  21. Diamantis N. Banerji U. Antibody-drug conjugates—an emerging class of cancer treatment. Br. J. Cancer 2016 114 4 362 367 10.1038/bjc.2015.435 26742008
    [Google Scholar]
  22. Joubert N. Beck A. Dumontet C. Denevault-Sabourin C. Antibody–drug conjugates: The last decade. Pharmaceuticals 2020 13 9 245 10.3390/ph13090245 32937862
    [Google Scholar]
  23. Kostova V. Désos P. Starck J.B. Kotschy A. The Chemistry Behind ADCs. Pharmaceuticals 2021 14 5 442 10.3390/ph14050442 34067144
    [Google Scholar]
  24. Zhou C. Kuang M. Tao Y. Wang J. Luo Y. Fu Y. Chen Z. Liu Y. Li Z. Wu W. Wang L. Dou Y. Wang J. Hou Y. Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening. Cell. Stem. Cell. 2024 31 9 1359 1375.e8 10.1016/j.stem.2024.06.007 38955185
    [Google Scholar]
  25. Hobson A.D. Antibody drug conjugates beyond cytotoxic payloads. Prog. Med. Chem. 2023 62 1 59 10.1016/bs.pmch.2023.10.001 37981349
    [Google Scholar]
  26. Zhou J. Guo Z. Peng X. Wu B. Meng Q. Lu X. Feng L. Guo T. Chrysotoxine regulates ferroptosis and the PI3K/AKT/mTOR pathway to prevent cervical cancer. J. Ethnopharmacol. 2025 338 Pt 3 119126 10.1016/j.jep.2024.119126 39557107
    [Google Scholar]
  27. Rafiq S. Hackett C.S. Brentjens R.J. Engineering strategies to overcome the current roadblocks in CAR T cell therapy. Nat. Rev. Clin. Oncol. 2020 17 3 147 167 10.1038/s41571‑019‑0297‑y 31848460
    [Google Scholar]
  28. Peters C. Brown S. Antibody–drug conjugates as novel anti-cancer chemotherapeutics. Biosci. Rep. 2015 35 4 e00225 10.1042/BSR20150089 26182432
    [Google Scholar]
  29. Atashzar M.R. Baharlou R. Karami J. Abdollahi H. Rezaei R. Pourramezan F. Zoljalali Moghaddam S.H. Cancer stem cells: A review from origin to therapeutic implications. J. Cell. Physiol. 2020 235 2 790 803 10.1002/jcp.29044 31286518
    [Google Scholar]
  30. Sun Y. Song G.D. Sun N. Chen J.Q. Yang S.S. Slug overexpression induces stemness and promotes hepatocellular carcinoma cell invasion and metastasis. Oncol. Lett. 2014 7 6 1936 1940 10.3892/ol.2014.2037 24932263
    [Google Scholar]
  31. Zhao C Song W Wang J Tang X Jiang Z. Immunoadjuvant-functionalized metal-organic frameworks: Synthesis and applications in tumor immune modulation. Chem. Commun. 2025 61 1962 1977 10.1039/D4CC06510G
    [Google Scholar]
  32. Strietz J. Stepputtis S.S. Follo M. Bronsert P. Stickeler E. Maurer J. Human primary breast cancer stem cells are characterized by epithelial-mesenchymal plasticity. Int. J. Mol. Sci. 2021 22 4 1808 10.3390/ijms22041808 33670400
    [Google Scholar]
  33. Guo Z. Guan K. Bao M. He B. Lu J. LINC-PINT plays an anti-tumor role in nasopharyngeal carcinoma by binding to XRCC6 and affecting its function. Pathol. Res. Pract. 2024 260 155460 10.1016/j.prp.2024.155460 39032384
    [Google Scholar]
  34. Liu Q. Zhang H. Jiang X. Qian C. Liu Z. Luo D. Factors involved in cancer metastasis: A better understanding to “seed and soil” hypothesis. Mol. Cancer 2017 16 1 176 10.1186/s12943‑017‑0742‑4 29197379
    [Google Scholar]
  35. Yeh H.W. Hsu E.C. Lee S.S. Lang Y.D. Lin Y.C. Chang C.Y. Lee S.Y. Gu D.L. Shih J.H. Ho C.M. Chen C.F. Chen C.T. Tu P.H. Cheng C.F. Chen R.H. Yang R.B. Jou Y.S. PSPC1 mediates TGF-β1 autocrine signalling and Smad2/3 target switching to promote EMT, stemness and metastasis. Nat. Cell Biol. 2018 20 4 479 491 10.1038/s41556‑018‑0062‑y 29593326
    [Google Scholar]
  36. Yue Z. Yuan Z. Zeng L. Wang Y. Lai L. Li J. Sun P. Xue X. Qi J. Yang Z. Zheng Y. Fang Y. Li D. Siwko S. Li Y. Luo J. Liu M. LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells. FASEB J. 2018 32 5 2422 2437 10.1096/fj.201700897R 29269400
    [Google Scholar]
  37. Lyu Z. Xin M. Oyston D.R. Xue T. Kang H. Wang X. Wang Z. Li Q. Cause and consequence of heterogeneity in human mesenchymal stem cells: Challenges in clinical application. Pathol. Res. Pract. 2024 260 155354 10.1016/j.prp.2024.155354 38870711
    [Google Scholar]
  38. Sasso J.M. Tenchov R. Bird R. Iyer K.A. Ralhan K. Rodriguez Y. Zhou Q.A. The evolving landscape of antibody–drug conjugates: In depth analysis of recent research progress. Bioconjug. Chem. 2023 34 11 1951 2000 10.1021/acs.bioconjchem.3c00374 37821099
    [Google Scholar]
  39. Rejili M. Synergistic strategies: ADC-PARP inhibitor combinations in triple-negative breast cancer therapy. Pathol. Res. Pract. 2025 272 156075 10.1016/j.prp.2025.156075
    [Google Scholar]
  40. Lu J. Jiang F. Lu A. Zhang G. Linkers having a crucial role in antibody–drug conjugates. Int. J. Mol. Sci. 2016 17 4 561 10.3390/ijms17040561 27089329
    [Google Scholar]
  41. Gupta G. Hussain M.S. Pant K. Ali H. Thapa R. Bhat A.A. Antibody-drug conjugates (ADCs): A novel therapy for triple-negative breast cancer (TNBC). Curr. Cancer Drug Targets 2025 25 2 108 112 10.2174/0115680096343056240828190900 39248064
    [Google Scholar]
  42. Lucas A.T. Moody A. Schorzman A.N. Zamboni W.C. Importance and considerations of antibody engineering in antibody-drug conjugates development from a clinical pharmacologist's perspective. Antibodies 2021 10 3 30 10.3390/antib10030030 34449544
    [Google Scholar]
  43. Drago J.Z. Modi S. Chandarlapaty S. Unlocking the potential of antibody–drug conjugates for cancer therapy. Nat. Rev. Clin. Oncol. 2021 18 6 327 344 10.1038/s41571‑021‑00470‑8 33558752
    [Google Scholar]
  44. Jiang X. Nik Nabil W.N. Ze Y. Dai R. Xi Z. Xu H. Unlocking natural potential: Antibody-drug conjugates with naturally derived payloads for cancer therapy. Phytother. Res. 2024 39688127
    [Google Scholar]
  45. Flygare J.A. Pillow T.H. Aristoff P. Antibody-drug conjugates for the treatment of cancer. Chem. Biol. Drug Des. 2013 81 1 113 121 10.1111/cbdd.12085 23253133
    [Google Scholar]
  46. Donaghy H. Effects of antibody, drug and linker on the preclinical and clinical toxicities of antibody-drug conjugates. MAbs 2016 8 4 659 671 10.1080/19420862.2016.1156829 27045800
    [Google Scholar]
  47. Giugliano F. Corti C. Tarantino P. Michelini F. Curigliano G. Bystander effect of antibody–drug conjugates: Fact or fiction? Curr. Oncol. Rep. 2022 24 7 809 817 10.1007/s11912‑022‑01266‑4 35305211
    [Google Scholar]
  48. Samantasinghar A. Sunildutt NP Ahmed F. Soomro AM. Salih ARC. Parihar P. A comprehensive review of key factors affecting the efficacy of antibody drug conjugate. Biomed Pharmacother 2023 161 114408 10.1016/j.biopha.2023.114408 36841027
    [Google Scholar]
  49. Criscitiello C. Morganti S. Curigliano G. Antibody- drug conjugates in solid tumors: A look into novel targets. J. Hematol. Oncol. 2021 14 1 20 10.1186/s13045‑021‑01035‑z 33509252
    [Google Scholar]
  50. Fu Z. Li S. Han S. Shi C. Zhang Y. Antibody drug conjugate: The “biological missile” for targeted cancer therapy. Signal Transduct. Target. Ther. 2022 7 1 93 10.1038/s41392‑022‑00947‑7 35318309
    [Google Scholar]
  51. Najminejad Z. Dehghani F. Mirzaei Y. Mer AH. Saghi SA. Abdolvahab MH. Clinical perspective: Antibody-drug conjugates for the treatment of HER2-positive breast cancer. Mol Ther 2023 31 7 1874 1903 10.1016/j.ymthe.2023.03.019 36950736
    [Google Scholar]
  52. Desai A. Abdayem P. Adjei A.A. Planchard D. Antibody-drug conjugates: A promising novel therapeutic approach in lung cancer. Lung Cancer 2022 163 96 106 10.1016/j.lungcan.2021.12.002 34942494
    [Google Scholar]
  53. Khongorzul P. Ling C.J. Khan F.U. Ihsan A.U. Zhang J. Antibody–drug conjugates: A comprehensive review. Mol. Cancer Res. 2020 18 1 3 19 10.1158/1541‑7786.MCR‑19‑0582 31659006
    [Google Scholar]
  54. Birrer M.J. Moore K.N. Betella I. Bates R.C. Antibody-drug conjugate-based therapeutics: State of the science. J. Natl. Cancer Inst. 2019 111 6 538 549 10.1093/jnci/djz035 30859213
    [Google Scholar]
  55. Staudacher A.H. Brown M.P. Antibody drug conjugates and bystander killing: Is antigen-dependent internalisation required? Br. J. Cancer 2017 117 12 1736 1742 10.1038/bjc.2017.367 29065110
    [Google Scholar]
  56. Shastry M. Gupta A. Chandarlapaty S. Young M. Powles T. Hamilton E. Rise of antibody-drug conjugates: The present and future. Am. Soc. Clin. Oncol. Educ. Book. 2023 43 e390094 10.1200/EDBK_390094 37229614
    [Google Scholar]
  57. Tai Y.T. Mayes P.A. Acharya C. Zhong M.Y. Cea M. Cagnetta A. Craigen J. Yates J. Gliddon L. Fieles W. Hoang B. Tunstead J. Christie A.L. Kung A.L. Richardson P. Munshi N.C. Anderson K.C. Novel anti–B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood 2014 123 20 3128 3138 10.1182/blood‑2013‑10‑535088 24569262
    [Google Scholar]
  58. Radocha J. van de Donk N.W.C.J. Weisel K. Monoclonal antibodies and antibody drug conjugates in multiple myeloma. Cancers 2021 13 7 1571 10.3390/cancers13071571 33805481
    [Google Scholar]
  59. Zhang M. Atkinson R.L. Rosen J.M. Selective targeting of radiation-resistant tumor-initiating cells. Proc. Natl. Acad. Sci. USA 2010 107 8 3522 3527 10.1073/pnas.0910179107 20133717
    [Google Scholar]
  60. Shmelkov S.V. Butler J.M. Hooper A.T. Hormigo A. Kushner J. Milde T. St Clair R. Baljevic M. White I. Jin D.K. Chadburn A. Murphy A.J. Valenzuela D.M. Gale N.W. Thurston G. Yancopoulos G.D. D’Angelica M. Kemeny N. Lyden D. Rafii S. CD133 expression is not restricted to stem cells, and both CD133+ and CD133- metastatic colon cancer cells initiate tumors. J. Clin. Invest. 2008 118 6 2111 2120 10.1172/JCI34401 18497886
    [Google Scholar]
  61. Kirchhoff D. Stelte-Ludwig B. Lerchen H.G. Wengner A.M. Ahsen O. Buchmann P. Märsch S. Mahlert C. Greven S. Dietz L. Erkelenz M. Zierz R. Johanssen S. Mumberg D. Sommer A. IL3RA-targeting antibody–drug conjugate BAY-943 with a kinesin spindle protein inhibitor payload shows efficacy in preclinical models of hematologic malignancies. Cancers 2020 12 11 3464 10.3390/cancers12113464 33233768
    [Google Scholar]
  62. Li Z. Fan J. Xiao Y. Wang W. Zhen C. Pan J. Wu W. Liu Y. Chen Z. Yan Q. Zeng H. Luo S. Liu L. Tu Z. Zhao X. Hou Y. Essential role of Dhx16-mediated ribosome assembly in maintenance of hematopoietic stem cells. Leukemia 2024 38 12 2699 2708 10.1038/s41375‑024‑02423‑3 39333759
    [Google Scholar]
  63. Ertas Y.N. Abedi Dorcheh K. Akbari A. Jabbari E. Nanoparticles for targeted drug delivery to cancer stem cells: A review of recent advances. Nanomaterials 2021 11 7 1755 10.3390/nano11071755 34361141
    [Google Scholar]
  64. Beck A. Goetsch L. Dumontet C. Corvaïa N. Strategies and challenges for the next generation of antibody–drug conjugates. Nat. Rev. Drug Discov. 2017 16 5 315 337 10.1038/nrd.2016.268 28303026
    [Google Scholar]
  65. Chau C.H. Steeg P.S. Figg W.D. Antibody–drug conjugates for cancer. Lancet 2019 394 10200 793 804 10.1016/S0140‑6736(19)31774‑X 31478503
    [Google Scholar]
  66. Birru B. Durthi C.P. Kacham S. Pola M. Rajulapati S.B. Parcha S.R. Kamal M.A. Stem cells in tumour microenvironment aid in prolonged survival rate of cancer cells and developed drug resistance: Major challenge in osteosarcoma treatment. Curr. Drug Metab. 2020 21 1 44 52 10.2174/1389200221666200214120226 32056519
    [Google Scholar]
  67. Smith L.M. Nesterova A. Ryan M.C. Duniho S. Jonas M. Anderson M. Zabinski R.F. Sutherland M.K. Gerber H-P. Van Orden K.L. Moore P.A. Ruben S.M. Carter P.J. CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers. Br. J. Cancer 2008 99 1 100 109 10.1038/sj.bjc.6604437 18542072
    [Google Scholar]
  68. Tong G. Peng T. Chen Y. Sha L. Dai H. Xiang Y. Zou Z. He H. Wang S. Effects of GLP-1 receptor agonists on biological behavior of colorectal cancer cells by regulating PI3K/AKT/mTOR signaling pathway. Front. Pharmacol. 2022 13 901559 10.3389/fphar.2022.901559 36034798
    [Google Scholar]
  69. Decary S. Berne P.F. Nicolazzi C. Lefebvre A.M. Dabdoubi T. Cameron B. Rival P. Devaud C. Prades C. Bouchard H. Cassé A. Henry C. Amara C. Brillac C. Ferrari P. Maçon L. Lacoste E. Combeau C. Beys E. Naimi S. García-Echeverría C. Mayaux J.F. Blanc V. Preclinical activity of SAR408701: A novel anti-CEACAM5–maytansinoid antibody–drug conjugate for the treatment of CEACAM5-positive epithelial tumors. Clin. Cancer Res. 2020 26 24 6589 6599 10.1158/1078‑0432.CCR‑19‑4051 33046521
    [Google Scholar]
  70. Izycka N. Rucinski M. Andrzejewska M. Szubert S. Nowak-Markwitz E. Sterzynska K. The prognostic value of cancer stem cell markers (CSCs) expression—ALDH1A1, CD133, CD44—For survival and long-term follow-up of ovarian cancer patients. Int. J. Mol. Sci. 2023 24 3 2400 10.3390/ijms24032400 36768723
    [Google Scholar]
  71. Frąszczak K. Barczyński B. The role of cancer stem cell markers in ovarian cancer. Cancers 2023 16 1 40 10.3390/cancers16010040 38201468
    [Google Scholar]
  72. Toledo-Guzmán M.E. Hernández M.I. Gómez-Gallegos Á.A. Ortiz-Sánchez E. ALDH as a stem cell marker in solid tumors. Curr. Stem Cell Res. Ther. 2019 14 5 375 388 10.2174/1574888X13666180810120012 30095061
    [Google Scholar]
  73. Sun D. Li X. Nie S. Liu J. Wang S. Disorders of cancer metabolism: The therapeutic potential of cannabinoids. Biomed. Pharmacother. 2023 157 113993 10.1016/j.biopha.2022.113993 36379120
    [Google Scholar]
  74. Hertweck M.K. Erdfelder F. Kreuzer K.A. CD44 in hematological neoplasias. Ann. Hematol. 2011 90 5 493 508 10.1007/s00277‑011‑1161‑z 21258793
    [Google Scholar]
  75. Moghaddam S.A. Yousefi B. Sanooghi D. Faghihi F. Hayati Roodbari N. Bana N. Joghataei M.T. Pooyan P. Arjmand B. Differentiation potential of human CD133 positive hematopoietic stem cells into motor neuron- like cells, in vitro . J. Chem. Neuroanat. 2017 86 35 40 10.1016/j.jchemneu.2017.07.006 28754612
    [Google Scholar]
  76. Najafi M. Farhood B. Mortezaee K. Kharazinejad E. Majidpoor J. Ahadi R. Hypoxia in solid tumors: A key promoter of cancer stem cell (CSC) resistance. J. Cancer Res. Clin. Oncol. 2020 146 1 19 31 10.1007/s00432‑019‑03080‑1 31734836
    [Google Scholar]
  77. Lin Y. Li H. Zheng S. Han R. Wu K. Tang S. Zhong X. Chen J. Elucidating tobacco smoke-induced craniofacial deformities: Biomarker and MAPK signaling dysregulation unraveled by cross-species multi-omics analysis. Ecotoxicol. Environ. Saf. 2024 288 117343 10.1016/j.ecoenv.2024.117343 39549573
    [Google Scholar]
  78. Deonarain M.P. Kousparou C.A. Epenetos A.A. Antibodies targeting cancer stem cells: A new paradigm in immunotherapy? MAbs 2009 1 1 12 25 10.4161/mabs.1.1.7347 20046569
    [Google Scholar]
  79. Sneha S. Nagare R.P. Priya S.K. Sidhanth C. Pors K. Ganesan T.S. Therapeutic antibodies against cancer stem cells: A promising approach. Cancer Immunol. Immunother. 2017 66 11 1383 1398 10.1007/s00262‑017‑2049‑0 28840297
    [Google Scholar]
  80. Wang K. Ning S. Zhang S. Jiang M. Huang Y. Pei H. Extracellular matrix stiffness regulates colorectal cancer progression via HSF4. J Exp Clin Cancer Res 2025 44 1 30 10.1186/s13046‑025‑03297‑8 39881364
    [Google Scholar]
  81. Marcucci F. Caserta C.A. Romeo E. Rumio C. Antibody-drug conjugates (ADC) against cancer stem-like cells (CSC)—Is there still room for optimism? Front. Oncol. 2019 9 167 10.3389/fonc.2019.00167 30984612
    [Google Scholar]
  82. Wang Y. Xu Y. Song J. Liu X. Liu S. Yang N. Wang L. Liu Y. Zhao Y. Zhou W. Zhang Y. Tumor cell-targeting and tumor microenvironment–responsive nanoplatforms for the multimodal imaging-guided photodynamic/photothermal/chemodynamic treatment of cervical cancer. Int. J. Nanomedicine 2024 19 5837 5858 10.2147/IJN.S466042 38887692
    [Google Scholar]
  83. Klein C. Brinkmann U. Reichert J.M. Kontermann R.E. The present and future of bispecific antibodies for cancer therapy. Nat. Rev. Drug Discov. 2024 23 4 301 319 10.1038/s41573‑024‑00896‑6 38448606
    [Google Scholar]
  84. Dumontet C. Reichert J.M. Senter P.D. Lambert J.M. Beck A. Antibody–drug conjugates come of age in oncology. Nat. Rev. Drug Discov. 2023 22 8 641 661 10.1038/s41573‑023‑00709‑2 37308581
    [Google Scholar]
  85. Leyton J.V. The endosomal-lysosomal system in ADC design and cancer therapy. Expert Opin. Biol. Ther. 2023 23 11 1067 1076 10.1080/14712598.2023.2285996 37978880
    [Google Scholar]
  86. Gutierrez M. Long G.V. Friedman C.F. Richards D.A. Corr B. Bastos B.R. Uemura M.I. Conkling P.R. Moreno V. Edenfield W.J. Becerra C.R. Piha-Paul S.A. Peterson A.C. Brown M. James L.P. Zheng M. Jiang J. Kollia G. Swijter A. Ascierto P.A. Anti-CTLA-4 probody BMS-986249 alone or in combination with nivolumab in patients with advanced cancers: Initial phase I results. J. Clin. Oncol. 2020 38 15_suppl 3058 10.1200/JCO.2020.38.15_suppl.3058
    [Google Scholar]
  87. Gutierrez M. Friedman C.F. Long G.V. Ascierto P.A. Melero I. Richards D. Bastos B.R. Moreno Garcia V. Uemura M. Conkling P. Corr B.R. Kim A.M. Zhu L. Hammell A. Perumal D. Chouzy A. Benavente F. Awosemo O. Hannah A. Le D.T. 740P Anti-cytotoxic T-lymphocyte antigen-4 (CTLA 4) probody BMS-986249 ± nivolumab (NIVO) in patients (pts) with advanced cancers: Updated phase I results. Ann. Oncol. 2022 33 S882 10.1016/j.annonc.2022.07.866
    [Google Scholar]
  88. Zammarchi F. Reinert H.W. Janghra N. Corbett S. Mellinas-Gomez M. Chowdhury S. Arora N. Tyrer P. Bertelli F. Williams D.G. Howard P.W. Hartley J.A. Berkel P.H. Abstract 52: Mechanistic and benchmarking studies of ADCT-502, a pyrrolobenzodiazepine (PBD) dimer-containing antibody-drug conjugate (ADC) targeting HER2-expressing solid tumors. Cancer Res. 2017 77 13_Supplement 52 10.1158/1538‑7445.AM2017‑52
    [Google Scholar]
  89. Engelhardt J. Akter R. Loffredo J. Bezman N. So P. Tipton K. Irving B. West J. Freebern W. Bunch T. Price K. Abstract 4551: Preclinical characterization of novel anti-CTLA-4 prodrug antibodies with an enhanced therapeutic index. Cancer Res. 2020 80 16_Supplement 4551 10.1158/1538‑7445.AM2020‑4551
    [Google Scholar]
  90. Saygin C. Matei D. Majeti R. Reizes O. Lathia J.D. Targeting cancer stemness in the clinic: From hype to hope. Cell Stem Cell 2019 24 1 25 40 10.1016/j.stem.2018.11.017 30595497
    [Google Scholar]
  91. Yang L. Shi P. Zhao G. Xu J. Peng W. Zhang J. Zhang G. Wang X. Dong Z. Chen F. Cui H. Targeting cancer stem cell pathways for cancer therapy. Signal Transduct. Target. Ther. 2020 5 1 8 10.1038/s41392‑020‑0110‑5 32296030
    [Google Scholar]
  92. Werbowetski-Ogilvie T.E. From sorting to sequencing in the molecular era: The evolution of the cancer stem cell model in medulloblastoma. FEBS J. 2022 289 7 1765 1778 10.1111/febs.15817 33714236
    [Google Scholar]
  93. Kim H.J. Cantor H. Cosmopoulos K. Overcoming immune checkpoint blockade resistance via EZH2 inhibition. Trends Immunol. 2020 41 10 948 963 10.1016/j.it.2020.08.010 32976740
    [Google Scholar]
  94. Nayak A. Warrier N.M. Kumar P. Cancer stem cells and the tumor microenvironment: Targeting the critical crosstalk through nanocarrier systems. Stem Cell Rev. Rep. 2022 18 7 2209 2233 10.1007/s12015‑022‑10426‑9 35876959
    [Google Scholar]
  95. Mohd-Zahid M.H. Mohamud R. Abdullah C.A.C. Lim J. Alem H. Hanaffi W.N.W. Colorectal cancer stem cells: A review of targeted drug delivery by gold nanoparticles. RSC Advances 2020 10 973 985 10.1039/C9RA08192E
    [Google Scholar]
  96. Pospieszna J. Dams-Kozlowska H. Udomsak W. Murias M. Kucinska M. Unmasking the deceptive nature of cancer stem cells: The role of CD133 in revealing their secrets. Int. J. Mol. Sci. 2023 24 13 10910 10.3390/ijms241310910 37446085
    [Google Scholar]
  97. Iturrioz-Rodríguez N. Sampron N. Matheu A. Current advances in temozolomide encapsulation for the enhancement of glioblastoma treatment. Theranostics 2023 13 9 2734 2756 10.7150/thno.82005 37284445
    [Google Scholar]
  98. Yin W. Pham C.V. Wang T. Al Shamaileh H. Chowdhury R. Patel S. Li Y. Kong L. Hou Y. Zhu Y. Chen S. Xu H. Jia L. Duan W. Xiang D. Inhibition of autophagy promotes the elimination of liver cancer stem cells by CD133 aptamer-targeted delivery of doxorubicin. Biomolecules 2022 12 11 1623 10.3390/biom12111623 36358973
    [Google Scholar]
  99. Attarian F. Hatamian G. Nosrati S. Akbari Oryani M. Javid H. Hashemzadeh A. Tarin M. Role of liposomes in chemoimmunotherapy of breast cancer. J. Drug Target. 2025 ••• 1 29 10.1080/1061186X.2025.2467139 39967479
    [Google Scholar]
  100. Xu H. Niu M. Yuan X. Wu K. Liu A. CD44 as a tumor biomarker and therapeutic target. Exp. Hematol. Oncol. 2020 9 1 36 10.1186/s40164‑020‑00192‑0 33303029
    [Google Scholar]
  101. Chen C. Zhao S. Karnad A. Freeman J.W. The biology and role of CD44 in cancer progression: Therapeutic implications. J. Hematol. Oncol. 2018 11 1 64 10.1186/s13045‑018‑0605‑5 29747682
    [Google Scholar]
  102. Martin-Castillo B. Lopez-Bonet E. Cuyàs E. Viñas G. Pernas S. Dorca J. Menendez J.A. Cancer stem cell-driven efficacy of trastuzumab (Herceptin): Towards a reclassification of clinically HER2-positive breast carcinomas. Oncotarget 2015 6 32 32317 32338 10.18632/oncotarget.6094 26474458
    [Google Scholar]
  103. Köseer A.S. Di Gaetano S. Arndt C. Bachmann M. Dubrovska A. Immunotargeting of cancer stem cells. Cancers 2023 15 5 1608 10.3390/cancers15051608 36900399
    [Google Scholar]
  104. Platt V.M. Szoka F.C. Jr. Anticancer therapeutics: Targeting macromolecules and nanocarriers to hyaluronan or CD44, a hyaluronan receptor. Mol. Pharm. 2008 5 4 474 486 10.1021/mp800024g 18547053
    [Google Scholar]
  105. Sauter A. Kloft C. Gronau S. Bogeschdorfer F. Erhardt T. Golze W. Schroen C. Staab A. Riechelmann H. Hoermann K. Pharmacokinetics, immunogenicity and safety of bivatuzumab mertansine, a novel CD44v6-targeting immunoconjugate, in patients with squamous cell carcinoma of the head and neck. Int. J. Oncol. 2007 30 4 927 935 10.3892/ijo.30.4.927 17332932
    [Google Scholar]
  106. MacLean M.R. Walker O.L. Arun R.P. Fernando W. Marcato P. Informed by cancer stem cells of solid tumors: Advances in treatments targeting tumor-promoting factors and pathways. Int. J. Mol. Sci. 2024 25 7 4102 10.3390/ijms25074102 38612911
    [Google Scholar]
  107. Chis A.A. Arseniu A.M. Morgovan C. Dobrea C.M. Frum A. Juncan A.M. Butuca A. Ghibu S. Gligor F.G. Rus L.L. Biopolymeric prodrug systems as potential antineoplastic therapy. Pharmaceutics 2022 14 9 1773 10.3390/pharmaceutics14091773 36145522
    [Google Scholar]
  108. Rastin F. Javid H. Oryani M.A. Rezagholinejad N. Afshari A.R. Karimi-Shahri M. Immunotherapy for colorectal cancer: Rational strategies and novel therapeutic progress. Int. Immunopharmacol. 2024 126 111055 10.1016/j.intimp.2023.111055 37992445
    [Google Scholar]
  109. Keller L. Werner S. Pantel K. Biology and clinical relevance of EpCAM. Cell Stress 2019 3 6 165 180 10.15698/cst2019.06.188 31225512
    [Google Scholar]
  110. Zhang Y. Wang Y. Uslu S. Venkatachalapathy S. Rashidian M. Schaefer J.V. Plückthun A. Distefano M.D. Enzymatic construction of DARPin-based targeted delivery systems using protein farnesyltransferase and a capture and release strategy. Int. J. Mol. Sci. 2022 23 19 11537 10.3390/ijms231911537 36232839
    [Google Scholar]
  111. Li G. Suzuki H. Ohishi T. Asano T. Tanaka T. Yanaka M. Nakamura T. Yoshikawa T. Kawada M. Kaneko M. Kato Y. Antitumor activities of a defucosylated anti-EpCAM monoclonal antibody in colorectal carcinoma xenograft models. Int. J. Mol. Med. 2023 51 2 18 10.3892/ijmm.2023.5221 36660940
    [Google Scholar]
  112. Satofuka H. Wang Y. Yamazaki K. Hamamichi S. Fukuhara T. Rafique A. Osako N. Kanazawa I. Endo T. Miyake N. Honma K. Nagashima Y. Hichiwa G. Shimoya K. Abe S. Moriwaki T. Murakami Y. Gao X. Kugoh H. Oshimura M. Ito Y. Kazuki Y. Characterization of human anti-EpCAM antibodies for developing an antibody–drug conjugate. Sci. Rep. 2023 13 1 4225 10.1038/s41598‑023‑31263‑x 36918661
    [Google Scholar]
  113. Hoimes CJ. Rosenberg JE. Petrylak DP. Carret A-S. Melhem-Bertrandt A. Flaig TW. Abstract A23: The EV-103 Trial: Enfortumab vedotin plus pembrolizumab and/or chemotherapy for patients with locally advanced or metastatic urothelial cancer. Clin. Cancer. Res. 2020 26 15_Supplement A23 10.1158/1557‑3265.BLADDER19‑A23
    [Google Scholar]
  114. Cheson B.D. Bartlett N.L. LaPlant B. Lee H.J. Advani R.J. Christian B. Diefenbach C.S. Feldman T.A. Ansell S.M. Brentuximab vedotin plus nivolumab as first-line therapy in older or chemotherapy-ineligible patients with Hodgkin lymphoma (ACCRU): A multicentre, single-arm, phase 2 trial. Lancet Haematol. 2020 7 11 e808 e815 10.1016/S2352‑3026(20)30275‑1 33010817
    [Google Scholar]
  115. Saini K.S. Punie K. Twelves C. Bortini S. de Azambuja E. Anderson S. Criscitiello C. Awada A. Loi S. Antibody-drug conjugates, immune-checkpoint inhibitors, and their combination in breast cancer therapeutics. Expert Opin. Biol. Ther. 2021 21 7 945 962 10.1080/14712598.2021.1936494 34043927
    [Google Scholar]
  116. Rastin F. Oryani M.A. Iranpour S. Javid H. Hashemzadeh A. Karimi-Shahri M. A new era in cancer treatment: Harnessing ZIF-8 nanoparticles for PD-1 inhibitor delivery. J. Mater. Chem. B Mater. Biol. Med. 2024 12 4 872 894 10.1039/D3TB02471G 38193564
    [Google Scholar]
  117. Shishparenok A.N. Furman V.V. Zhdanov D.D. DNA-based nanomaterials as drug delivery platforms for increasing the effect of drugs in tumors. Cancers 2023 15 7 2151 10.3390/cancers15072151 37046816
    [Google Scholar]
  118. Akbari Oryani M. Tarin M. Rahnama Araghi L. Rastin F. Javid H. Hashemzadeh A. Karimi-Shahri M. Synergistic cancer treatment using porphyrin-based metal-organic Frameworks for photodynamic and photothermal therapy. J. Drug Target. 2025 33 4 473 491 10.1080/1061186X.2024.2433551 39618308
    [Google Scholar]
  119. Nguyen A.L. Facey C.O.B. Boman B.M. The Significance of Aldehyde Dehydrogenase 1 in Cancers. Int. J. Mol. Sci. 2024 26 1 251 10.3390/ijms26010251 39796106
    [Google Scholar]
  120. Visus C. Wang Y. Lozano-Leon A. Ferris R.L. Silver S. Szczepanski M.J. Brand R.E. Ferrone C.R. Whiteside T.L. Ferrone S. DeLeo A.B. Wang X. Targeting ALDH(bright) human carcinoma-initiating cells with ALDH1A1-specific CD8+ T cells. Clin. Cancer Res. 2011 17 19 6174 6184 10.1158/1078‑0432.CCR‑11‑1111 21856769
    [Google Scholar]
  121. Cannon P. Asokan A. Czechowicz A. Hammond P. Kohn D.B. Lieber A. Malik P. Marks P. Porteus M. Verhoeyen E. Weissman D. Weissman I. Kiem H.P. Safe and effective in vivo targeting and gene editing in hematopoietic stem Cells: Strategies for accelerating development. Hum. Gene Ther. 2021 32 1-2 31 42 10.1089/hum.2020.263 33427035
    [Google Scholar]
  122. Garza Treviño E.N. Quiroz Reyes A.G. Rojas Murillo J.A. de la Garza Kalife D.A. Delgado Gonzalez P. Islas J.F. Estrada Rodriguez A.E. Gonzalez Villarreal C.A. Cell therapy as target therapy against colon cancer stem cells. Int. J. Mol. Sci. 2023 24 9 8163 10.3390/ijms24098163 37175871
    [Google Scholar]
  123. Hussain M.S. Bisht A.S. Ali H. Gupta G. Advancing small nucleic acid drug delivery: From stability challenges to novel therapeutic applications. Curr. Drug Deliv. 2025 22 10.2174/0115672018370847250110094907 39817375
    [Google Scholar]
  124. Maqbool M. Hussain M.S. Shaikh N.K. Sultana A. Bisht A.S. Agrawal M. Noncoding RNAs in the COVID-19 saga: An untold story. Viral Immunol. 2024 37 6 269 286 10.1089/vim.2024.0026 38968365
    [Google Scholar]
  125. Gonzalez-Callejo P. Guo Z. Ziglari T. Claudio N.M. Nguyen K.H. Oshimori N. Seras-Franzoso J. Pucci F. Cancer stem cell-derived extracellular vesicles preferentially target MHC-II–macrophages and PD1+ T cells in the tumor microenvironment. PLoS One 2023 18 2 e0279400 10.1371/journal.pone.0279400 36735677
    [Google Scholar]
  126. Ramalingam P.S. Premkumar T. Sundararajan V. Hussain M.S. Arumugam S. Design and development of dual targeting CAR protein for the development of CAR T-cell therapy against KRAS mutated pancreatic ductal adenocarcinoma using computational approaches. Discover Oncology 2024 15 1 592 10.1007/s12672‑024‑01455‑6 39453574
    [Google Scholar]
  127. Ahmed N. Brawley V.S. Hegde M. Robertson C. Ghazi A. Gerken C. Liu E. Dakhova O. Ashoori A. Corder A. Gray T. Wu M.F. Liu H. Hicks J. Rainusso N. Dotti G. Mei Z. Grilley B. Gee A. Rooney C.M. Brenner M.K. Heslop H.E. Wels W.S. Wang L.L. Anderson P. Gottschalk S. Human epidermal growth factor receptor 2 (HER2) –Specific chimeric antigen receptor–Modified T cells for the immunotherapy of HER2-positive sarcoma. J. Clin. Oncol. 2015 33 15 1688 1696 10.1200/JCO.2014.58.0225 25800760
    [Google Scholar]
  128. Wu Y. Li J. Jabbarzadeh Kaboli P. Shen J. Wu X. Zhao Y. Ji H. Du F. Zhou Y. Wang Y. Zhang H. Yin J. Wen Q. Cho C.H. Li M. Xiao Z. Natural killer cells as a double-edged sword in cancer immunotherapy: A comprehensive review from cytokine therapy to adoptive cell immunotherapy. Pharmacol. Res. 2020 155 104691 10.1016/j.phrs.2020.104691 32070721
    [Google Scholar]
  129. Pietra G. Manzini C. Rivara S. Vitale M. Cantoni C. Petretto A. Balsamo M. Conte R. Benelli R. Minghelli S. Solari N. Gualco M. Queirolo P. Moretta L. Mingari M.C. Melanoma cells inhibit natural killer cell function by modulating the expression of activating receptors and cytolytic activity. Cancer Res. 2012 72 6 1407 1415 10.1158/0008‑5472.CAN‑11‑2544 22258454
    [Google Scholar]
  130. Xu Q. Liu G. Yuan X. Xu M. Wang H. Ji J. Konda B. Black K.L. Yu J.S. Antigen-specific T-cell response from dendritic cell vaccination using cancer stem- like cell-associated antigens. Stem Cells 2009 27 8 1734 1740 10.1002/stem.102 19536809
    [Google Scholar]
  131. Zhao Q. Zong H. Zhu P. Su C. Tang W. Chen Z. Jin S. Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs. Exp. Hematol. Oncol. 2024 13 1 6 10.1186/s40164‑024‑00474‑x 38254219
    [Google Scholar]
  132. Borlongan M.C. Saha D. Wang H. Tumor microenvironment: A Niche for cancer stem cell immunotherapy. Stem Cell Rev. Rep. 2024 20 1 3 24 10.1007/s12015‑023‑10639‑6 37861969
    [Google Scholar]
  133. Li Z. CD133: A stem cell biomarker and beyond. Exp. Hematol. Oncol. 2013 2 1 17 10.1186/2162‑3619‑2‑17 23815814
    [Google Scholar]
  134. Barzegar Behrooz A. Syahir A. Ahmad S. CD133: Beyond a cancer stem cell biomarker. J. Drug Target. 2019 27 3 257 269 10.1080/1061186X.2018.1479756 29911902
    [Google Scholar]
  135. Yan Y. Zuo X. Wei D. Concise review: Emerging role of CD44 in cancer stem cells: A promising biomarker and therapeutic target. Stem Cells Transl. Med. 2015 4 9 1033 1043 10.5966/sctm.2015‑0048 26136504
    [Google Scholar]
  136. Arabi L Badiee A Mosaffa F Jaafari MR Targeting CD44 expressing cancer cells with anti-CD44 monoclonal antibody improves cellular uptake and antitumor efficacy of liposomal doxorubicin. J Control Release 2015 220 Pt A 275 286 10.1016/j.jconrel.2015.10.044 26518722
    [Google Scholar]
  137. Glumac P.M. LeBeau A.M. The role of CD133 in cancer: A concise review. Clin. Transl. Med. 2018 7 1 e18 10.1186/s40169‑018‑0198‑1 29984391
    [Google Scholar]
  138. Cheng J.X. Liu B.L. Zhang X. How powerful is CD133 as a cancer stem cell marker in brain tumors? Cancer Treat. Rev. 2009 35 5 403 408 10.1016/j.ctrv.2009.03.002 19369008
    [Google Scholar]
  139. Hu Y. Zhou Y. Dai N. Song S. Zhao X. Zhao Y. Cheng L. Lu H. Ge J. Enhancing panvascular medicine: Unveiling the nexus of pan-cardio-oncology and expanding therapeutic frontiers. Sci. Bull. 2025 70 6 798 800 10.1016/j.scib.2025.01.016 39828464
    [Google Scholar]
  140. Stein E.M. Walter R.B. Erba H.P. Fathi A.T. Advani A.S. Lancet J.E. Ravandi F. Kovacsovics T. DeAngelo D.J. Bixby D. Faderl S. Jillella A.P. Ho P.A. O’Meara M.M. Zhao B. Biddle-Snead C. Stein A.S. A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33-positive acute myeloid leukemia. Blood 2018 131 4 387 396 10.1182/blood‑2017‑06‑789800 29196412
    [Google Scholar]
  141. Kantarjian H.M. DeAngelo D.J. Stelljes M. Martinelli G. Liedtke M. Stock W. Gökbuget N. O’Brien S. Wang K. Wang T. Paccagnella M.L. Sleight B. Vandendries E. Advani A.S. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N. Engl. J. Med. 2016 375 8 740 753 10.1056/NEJMoa1509277 27292104
    [Google Scholar]
  142. Rudin C.M. Pietanza M.C. Bauer T.M. Ready N. Morgensztern D. Glisson B.S. Byers L.A. Johnson M.L. Burris H.A. III Robert F. Han T.H. Bheddah S. Theiss N. Watson S. Mathur D. Vennapusa B. Zayed H. Lally S. Strickland D.K. Govindan R. Dylla S.J. Peng S.L. Spigel D.R. Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: A first-in-human, first-in-class, open-label, phase 1 study. Lancet Oncol. 2017 18 1 42 51 10.1016/S1470‑2045(16)30565‑4 27932068
    [Google Scholar]
  143. Chen S. Long S. Liu Y. Wang S. Hu Q. Fu L. Luo D. Evaluation of a three-gene methylation model for correlating lymph node metastasis in postoperative early gastric cancer adjacent samples. Front. Oncol. 2024 14 1432869 10.3389/fonc.2024.1432869 39484038
    [Google Scholar]
  144. Kharkar P.S. Cancer stem cell (CSC) inhibitors in oncology—A promise for a better therapeutic outcome: State of the art and future perspectives. J. Med. Chem. 2020 63 24 15279 15307 10.1021/acs.jmedchem.0c01336 33325699
    [Google Scholar]
  145. Chen I.J. Chuang C.H. Hsieh Y.C. Lu Y.C. Lin W.W. Huang C.C. Cheng T.C. Cheng Y.A. Cheng K.W. Wang Y.T. Chen F.M. Cheng T.L. Tzou S.C. Selective antibody activation through protease-activated pro-antibodies that mask binding sites with inhibitory domains. Sci. Rep. 2017 7 1 11587 10.1038/s41598‑017‑11886‑7 28912497
    [Google Scholar]
  146. Singh S. Serwer L. DuPage A. Elkins K. Chauhan N. Ravn M. Buchanan F. Wang L. Krimm M. Wong K. Sagert J. Tipton K. Moore S.J. Huang Y. Jang A. Ureno E. Miller A. Patrick S. Duvur S. Liu S. Vasiljeva O. Li Y. Henriques T. Badagnani I. Jeffries S. Schleyer S. Leanna R. Krebber C. Viswanathan S. Desnoyers L. Terrett J. Belvin M. Morgan-Lappe S. Kavanaugh W.M. Richardson J. Nonclinical efficacy and safety of CX-2029, an anti-CD71 probody–drug conjugate. Mol. Cancer Ther. 2022 21 8 1326 1336 10.1158/1535‑7163.MCT‑21‑0193 35666803
    [Google Scholar]
  147. Liu R. Wang R.E. Wang F. Antibody-drug conjugates for non-oncological indications. Expert Opin. Biol. Ther. 2016 16 5 591 593 10.1517/14712598.2016.1161753 26937991
    [Google Scholar]
  148. McPherson M.J. Hobson A.D. Pushing the envelope: Advancement of ADCs outside of oncology. Methods Mol. Biol. 2020 2078 23 36 10.1007/978‑1‑4939‑9929‑3_2 31643047
    [Google Scholar]
  149. Theocharopoulos C. Lialios P.P. Samarkos M. Gogas H. Ziogas D.C. Antibody-drug conjugates: Functional principles and applications in oncology and beyond. Vaccines 2021 9 10 1111 10.3390/vaccines9101111 34696218
    [Google Scholar]
  150. Pal L.B. Bule P. Khan W. Chella N. An overview of the development and preclinical evaluation of antibody- Drug conjugates for non-oncological applications. Pharmaceutics 2023 15 7 1807 10.3390/pharmaceutics15071807 37513995
    [Google Scholar]
/content/journals/cmc/10.2174/0109298673393449250818052754
Loading
Cancer Stem Cell-targeted Antibody-drug Conjugates for Cancer Immunotherapy
Bentham Science Publishers ; https://doi.org/10.2174/0109298673393449250818052754
/content/journals/cmc/10.2174/0109298673393449250818052754
/content/journals/cmc/10.2174/0109298673393449250818052754
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: precision oncology ; tumor microenvironment ; Cancer stem cells ; drug resistance ; targeted therapy ; antibody-drug conjugates ; immunotherapy

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test