Article ; Online: A Novel bispecific T-cell engager (BiTE) targeting CD22 and CD3 has both in vitro and in vivo activity and synergizes with blinatumomab in an acute lymphoblastic leukemia (ALL) tumor model.
Cancer immunology, immunotherapy : CII
2023 Volume 72, Issue 9, Page(s) 2939–2948
Abstract: Immunotherapy has revolutionized cancer therapy. Two recently FDA-approved immunotherapies for B-cell malignancies target CD19, in the form of a Bispecific T-Cell Engager (BiTE) antibody construct or chimeric antigen receptor T (CAR-T) cells. ... ...
| Abstract | Immunotherapy has revolutionized cancer therapy. Two recently FDA-approved immunotherapies for B-cell malignancies target CD19, in the form of a Bispecific T-Cell Engager (BiTE) antibody construct or chimeric antigen receptor T (CAR-T) cells. Blinatumomab, an FDA-approved BiTE, binds to CD19 on B cells and to CD3 on T cells, mediating effector-target cell contact and T-cell activation that results in effective elimination of target B cells. Although CD19 is expressed by essentially all B-cell malignancies at clinical presentation, relapses with loss or reduction in CD19 surface expression are increasingly recognized as a cause of treatment failure. Therefore, there is a clear need to develop therapeutics for alternate targets. We have developed a novel BiTE consisting of humanized anti-CD22 and anti-CD3 single chain variable fragments. Target binding of the anti-CD22 and anti-CD3 moieties was confirmed by flow cytometry. CD22-BiTE promoted in vitro cell-mediated cytotoxicity in a dose and effector: target (E:T)-dependent fashion. Additionally, in an established acute lymphoblastic leukemia (ALL) xenograft mouse model, CD22-BiTE demonstrated tumor growth inhibition, comparable to blinatumomab. Further, the combination of blinatumomab and CD22-BiTE yielded increased efficacy in vivo when compared to the single agents. In conclusion, we report here the development of a new BiTE with cytotoxic activity against CD22 |
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| MeSH term(s) | Humans ; Animals ; Mice ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Antineoplastic Agents/therapeutic use ; T-Lymphocytes ; Antibodies, Bispecific/pharmacology ; Antibodies, Bispecific/therapeutic use ; Antigens, CD19 |
| Chemical Substances | blinatumomab (4FR53SIF3A) ; Antineoplastic Agents ; Antibodies, Bispecific ; Antigens, CD19 |
| Language | English |
| Publishing date | 2023-05-29 |
| Publishing country | Germany |
| Document type | Journal Article |
| ZDB-ID | 195342-4 |
| ISSN | 1432-0851 ; 0340-7004 |
| ISSN (online) | 1432-0851 |
| ISSN | 0340-7004 |
| DOI | 10.1007/s00262-023-03444-0 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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