Bispecific antibodies for the treatment of lymphomas: Promises and challenges.

Hematological Oncology
Stephen J Schuster

Abstract

The potential of bispecific antibodies to direct antigen-specific T cell-mediated cytotoxicity toward malignant cells bearing a target antigen was recognized over 35 years ago. Generally, this is accomplished by combining a T-cell receptor-specific monoclonal antibody or monoclonal antibody-derived fragment that is capable of activating and expanding resting T cells with a second monoclonal antibody or monoclonal antibody fragment directed against a tumor target antigen. Bispecific antibodies induce effector T cells that bind to tumor cells independently of their T-cell receptor specificity and without the requirement of MHC-mediated antigen presentation, focusing effector T-cell cytotoxicity on tumor cells bearing the target antigen. The therapeutic efficacy of this approach for treatment of relapsed or refractory B-cell lymphomas was first demonstrated with blinatumomab, a single molecule comprised of two linked single-chain variable fragments with binding specificities for CD19 and CD3. The recent demonstration that chimeric antigen receptor (CAR) modified T cells can achieve very durable remissions in some patients with relapsed or refractory B-cell lymphomas, as well as the potential efficacy of bispecific antibodies in CA...Continue Reading

References

Apr 18, 1985·Nature·U D StaerzM J Bevan
Jan 1, 1964·The Journal of Experimental Medicine·H H FUDENBERGA NISONOFF
Feb 18, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Maria-Elisabeth GoebelerRalf C Bargou
Jan 11, 2017·MAbs·Ulrich Brinkmann, Roland E Kontermann
Oct 7, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kathryn M CappellJames N Kochenderfer
Feb 18, 2021·The New England Journal of Medicine·Elise A ChongUNKNOWN Lymphoma Program Investigators at the University of Pennsylvania

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