Skip to content
2000
Volume 20, Issue 2
  • ISSN: 1574-8863
  • E-ISSN: 2212-3911

Abstract

Bispecific antibodies (BsAbs) are promising immunotherapies for cancer treatment designed to engage both tumour and immune cells. However, their use is associated with potential toxicities, including cytokine release syndrome (CRS), neurotoxicity, and on-target, off-tumour toxicity. CRS, characterized by cytokine release, is the most common, potentially life-threatening toxicity. Neurotoxicity presents as neurological symptoms and on-target, off-tumour toxicity damages healthy cells. Incidence and severity vary based on BsAb type, dose, patient factors, and tumor characteristics. For this study, articles pertaining to BsAb toxicity were searched on PubMed.

Moreover, the management involves early recognition, dose modification, supportive care, and, in severe cases, immunosuppressive therapy or treatment discontinuation. Clinicians must carefully assess risks and benefits, considering individual patient profiles. Close monitoring and multidisciplinary collaboration are crucial for effective BsAb therapy. All in all, while toxicity is a concern, with vigilant management, BsAbs remain a valuable cancer treatment option.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cds/10.2174/0115748863286774240219094217
2025-05-01
2025-10-25

  • From This Site

    /content/journals/cds/10.2174/0115748863286774240219094217
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. TeacheyD.T. LaceyS.F. ShawP.A. Identification of predictive biomarkers for cytokine release syndrome after chimeric antigen receptor t-cell therapy for acute lymphoblastic leukemia.Cancer Discov.20166666467910.1158/2159‑8290.CD‑16‑0040 27076371
     [Google Scholar]
  2. SantomassoB.D. ParkJ.H. SalloumD. Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with b-cell acute lymphoblastic leukemia.Cancer Discov.20188895897110.1158/2159‑8290.CD‑17‑1319 29880584
     [Google Scholar]
  3. WeiS.C. AnangN.A.A.S. SharmaR. Combination anti–CTLA-4 plus anti–PD-1 checkpoint blockade utilizes cellular mechanisms partially distinct from monotherapies.Proc. Natl. Acad. Sci. USA201911645226992270910.1073/pnas.1821218116 31636208
     [Google Scholar]
  4. TolcherA.W. GordonM. MahoneyK.M. Phase 1 first-in-human study of dalutrafusp alfa, an anti–CD73-TGF-β-trap bifunctional antibody, in patients with advanced solid tumors.J. Immunother. Cancer2023112e00526710.1136/jitc‑2022‑005267 36746510
     [Google Scholar]
  5. CostaL.J. WongS.W. BermúdezA. First clinical study of the b-cell maturation antigen (bcma) 2+1 t cell engager (tce) teclistamab (jnj-64007957) in patients (pts) with relapsed and/or refractory multiple myeloma (r/r mm): Updated results of a phase 1 dose-escalation study (NCT03145181).Blood201913457010.1182/blood‑2019‑122895
     [Google Scholar]
  6. SallesG. DuellJ. González BarcaE. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): A multicentre, prospective, single-arm, phase 2 study.Lancet Oncol.202021797898810.1016/S1470‑2045(20)30225‑4 32511983
     [Google Scholar]
  7. LöfflerA. KuferP. LutterbüseR. A recombinant bispecific single-chain antibody, CD19 × CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes.Blood20009562098210310.1182/blood.V95.6.2098 10706880
     [Google Scholar]
  8. BrudnoJ.N. SomervilleR.P.T. ShiV. Allogeneic T cells that express an anti-cd19 chimeric antigen receptor induce remissions of b-cell malignancies that progress after allogeneic hematopoietic stem-cell transplantation without causing graft-versus-host disease.J. Clin. Oncol.201634101112112110.1200/JCO.2015.64.5929 26811520
     [Google Scholar]
  9. BrudnoJ.N. KochenderferJ.N. Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management.Blood Rev.201934455510.1016/j.blre.2018.11.002 30528964
     [Google Scholar]
  10. BrownP.A. JiL. XuX. A Randomized Phase III Trial of Blinatumomab vs Standard of Care in Pediatric Patients with First Relapse of B-Cell Acute Lymphoblastic Leukemia (B-ALL).Blood2020136Suppl. 31310.1182/blood‑2020‑139861
     [Google Scholar]
  11. HuY. TianZ. ZhangC. Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy.Acta Pharmacol. Sin.201839216717610.1038/aps.2017.125 28880014
     [Google Scholar]
  12. RafeiH. KantarjianH.M. JabbourE.J. Immunotherapy in acute lymphoblastic leukemia and lymphoma: Current status and future directions.Immunotherapy201791078780310.2217/imt‑2017‑0061
     [Google Scholar]
  13. LeeD.W. SantomassoB.D. LockeF.L. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells.Biol. Blood Marrow Transplant.201925462563810.1016/j.bbmt.2018.12.758 30592986
     [Google Scholar]
  14. LiuD. ZhaoJ. Cytokine release syndrome: Grading, modeling, and new therapy.J. Hematol. Oncol.201811112110.1186/s13045‑018‑0653‑x 30249264
     [Google Scholar]
  15. LandryK. ThomasA.A. Neurological Complications of CAR T Cell Therapy.Curr Oncol Rep.20202288310.1007/s11912‑020‑00935‑632607727
     [Google Scholar]
  16. LiuZ. ZhuY. XieH. ZouZ. Immune-mediated hepatitis induced by immune checkpoint inhibitors: Current updates and future perspectives.Front.Pharmacol202313107746810.3389/fphar.2022.1077468
     [Google Scholar]
  17. LöfflerM.W. ChandranS. MachJ.P. Bispecific T-cell engagers for cancer immunotherapy: A review.BioDrugs202034669371210.1007/s40259‑020‑00444‑w
     [Google Scholar]
  18. Shimabukuro-VornhagenA. GödelP. SubkleweM. Cytokine release syndrome.J. Immunother. Cancer2018615610.1186/s40425‑018‑0343‑9 29907163
     [Google Scholar]
  19. GauthierJ. TurtleC.J. Insights into cytokine release syndrome and neurotoxicity after CD19-specific CAR-T cell therapy.Curr. Res. Transl. Med.2018662505210.1016/j.retram.2018.03.003 29625831
     [Google Scholar]
  20. Clinical practice guidelines for the management of cytokine release syndrome and neurological toxicities associated with chimeric antigen receptor t cell therapy. American Society of Hematology.Blood Adv.20193234169419110.1182/bloodadvances.2019000962
     [Google Scholar]
  21. SalvarisR. OngJ. GregoryG.P. Bispecific antibodies: A review of development, clinical efficacy and toxicity in b-cell lymphomas.J. Pers. Med.202111535510.3390/jpm11050355 33946635
     [Google Scholar]
/content/journals/cds/10.2174/0115748863286774240219094217
Loading
Perils and Problems in Bispecific T-Cell Engager Antibodies
Curr Drug Saf 20, 85 (2025); https://doi.org/10.2174/0115748863286774240219094217
/content/journals/cds/10.2174/0115748863286774240219094217
/content/journals/cds/10.2174/0115748863286774240219094217
Loading

Data & Media loading...


  • Article Type:     Editorial
Keyword(s): bispecific antibodies; BsAbs; cytokine release syndrome; Immunotherapy; neurotoxic; toxicity

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