Bispecific antibodies for the treatment of lymphomas: Promises and challenges.
Hematol Oncol
; 39 Suppl 1: 113-116, 2021 Jun.
Article
em En
| MEDLINE
| ID: mdl-34105818
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 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 11 or 21 CD20CD3 Fab formats for treatment of relapsed or refractory B-cell lymphomas.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfoma de Células B
/
Anticorpos Biespecíficos
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Antineoplásicos Imunológicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article