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Preclinical characterization and comparison between CD3/CD19 bispecific and novel CD3/CD19/CD20 trispecific antibodies against B-cell acute lymphoblastic leukemia: targeted immunotherapy for acute lymphoblastic leukemia / 医学前沿
Frontiers of Medicine ; (4): 139-149, 2022.
Article in English | WPRIM | ID: wpr-929189
ABSTRACT
The CD19-targeting bispecific T-cell engager blinatumomab has shown remarkable efficacy in patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. However, several studies showed that blinatumomab has a short plasma half-life due to its low molecular weight, and thus its clinical use is limited. Furthermore, multiple trials have shown that approximately 30% of blinatumomab-relapsed cases are characterized by CD19 negative leukemic cells. Here, we design and characterize two novel antibodies, A-319 and A-2019. Blinatumomab and A-319 are CD3/CD19 bispecific antibodies with different molecular sizes and structures, and A-2019 is a novel CD3/CD19/CD20 trispecific antibody with an additional anti-CD20 function. Our in vitro, ex vivo, and in vivo experiments demonstrated that A-319 and A-2019 are potent antitumor agents and capable of recruiting CD3 positive T cells, enhancing T-cell function, mediating B-cell depletion, and eventually inhibiting tumor growth in Raji xenograft models. The two molecules are complementary in terms of efficacy and specificity profile. The activity of A-319 demonstrated superior to that of A-2019, whereas A-2019 has an additional capability to target CD20 in cells missing CD19, suggesting its potential function against CD19 weak or negative CD20 positive leukemic cells.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: T-Lymphocytes / Antigens, CD19 / Precursor Cell Lymphoblastic Leukemia-Lymphoma / Immunotherapy / Antineoplastic Agents Limits: Humans Language: English Journal: Frontiers of Medicine Year: 2022 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: T-Lymphocytes / Antigens, CD19 / Precursor Cell Lymphoblastic Leukemia-Lymphoma / Immunotherapy / Antineoplastic Agents Limits: Humans Language: English Journal: Frontiers of Medicine Year: 2022 Type: Article