CD-19-directed immunotherapy resistance mechanisms of B-precursor acute lymphoblastic leukemia
https://doi.org/10.17650/1818-8346-2019-13-4-27-36
Abstract
Immunotherapy is the most rapidly evolving field in clinical malignant hematology. Targeting of the B-lineage surface antigen CD19 in B-lineage acute lymphoblastic leukemia and B-cell lymphoma is a story of great success. Recently two approaches of CD19 immunotargeting were approved for clinical application: CD3 × CD19 bi-specific T-cell engager blinatumomab and CD19 chimeric antigen receptor (CAR) Tcells. Both approaches demonstrated an unprecedented activity in a cohort of patients with relapsed and refractory B-cell leukemia and lymphoma both in the adult and pediatric population. Early clinical research has showed that tumors are able to escape the immunological control and become resistant to the immune attack. Mechanisms of the tumor immune escape are being actively studied and include diverse pathways, such as alternative splicing of CD19 and immunosuppressive tumor microenvironment. Current review briefly summarizes data regarding the mechanisms of CD19-positive leukemia resistance to CD19 immune targeting and discusses potential approaches to overcome it.
About the Authors
E. V. Glukhanyuk
Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
Russian Federation
1 Samory Mashela St., Moscow 117997
Russian Federation
1 Samory Mashela St., Moscow 117997
A. V. Stepanov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
Russian Federation
16/10 Miklukho-Maklaya St., Moscow 117997
Russian Federation
16/10 Miklukho-Maklaya St., Moscow 117997
A. M. Popov
Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
Russian Federation
1 Samory Mashela St., Moscow 117997
Russian Federation
1 Samory Mashela St., Moscow 117997
M. A. Maschan
Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
Russian Federation
1 Samory Mashela St., Moscow 117997
Russian Federation
1 Samory Mashela St., Moscow 117997
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Review
For citations:
Glukhanyuk E.V., Stepanov A.V., Popov A.M., Maschan M.A. CD-19-directed immunotherapy resistance mechanisms of B-precursor acute lymphoblastic leukemia. Oncohematology. 2018;13(4):27-36. (In Russ.) https://doi.org/10.17650/1818-8346-2019-13-4-27-36
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