Bispecific antibodies for the treatment of lymphomas: Promises and challenges

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...

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Bibliographic Details
Published in:Hematological oncology 2021-06, Vol.39 (S1), p.113-116
Main Author: Schuster, Stephen J.
Format: Article
Language:English
Subjects:
Antigen presentation
Antigens
Bispecific antibodies
bispecific antibody
blinatumomab
CD19 antigen
CD20 antigen
CD3 antigen
Chimeric antigen receptors
Clinical trials
Cytotoxicity
Effector cells
glofitamab
immunotherapy
Lymphocytes
Lymphocytes B
Lymphocytes T
Lymphoma
Major histocompatibility complex
Monoclonal antibodies
mosunetuzumab
odronextumab
Receptors
Target recognition
Targeted cancer therapy
Toxicity
Tumor cells
Tumors
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Summary: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 CAR T cell failures, has rekindled interested in bispecific antibodies as a T cell‐mediated therapeutic approach. We review the early results of phase 1 clinical trials of bispecific antibodies targeting CD20 on B cells and engaging T cells via CD3 in 1:1 or 2:1 CD20:CD3 Fab formats for treatment of relapsed or refractory B‐cell lymphomas.
ISSN:0278-0232
1099-1069
DOI:10.1002/hon.2858