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Resistance to CART cell therapy: lessons learned from the treatment of hematological malignancies
- Source :
- Leukemia & Lymphoma. 62:2052-2063
- Publication Year :
- 2021
- Publisher :
- Informa UK Limited, 2021.
-
Abstract
- Chimeric antigen receptor T (CART) cell immunotherapy has yielded significant clinical success in treating certain hematological malignancies. However, despite high initial response rates, most patients eventually relapse. Resistance to CART cell therapy can stem from tumor cell mutations, T cell defects, and tumor microenvironment (TME) immunosuppression. Tumor cells can downregulate target antigen expression to evade CART cell detection or mutate death receptor pathways to resist CART cell cytotoxicity. Patient T cells can be intrinsically defective, and CART cells often undergo exhaustion. The TME is abundant with immunosuppressive cells and factors which contribute to suboptimal CART cell activity. Collectively, issues originating in tumor cells, T cells, and the TME present significant hurdles to long-term remission after CART cell therapy. Various strategies to combat CART cell resistance have shown promise in preclinical studies and early clinical trials and are crucial to achieving durable responses.
- Subjects :
- Cart
Cancer Research
medicine.medical_treatment
T cell
Cell
Cell- and Tissue-Based Therapy
Receptors, Antigen, T-Cell
Immunotherapy, Adoptive
Cell therapy
03 medical and health sciences
0302 clinical medicine
immune system diseases
parasitic diseases
mental disorders
Tumor Microenvironment
medicine
Humans
Tumor microenvironment
Receptors, Chimeric Antigen
business.industry
virus diseases
Immunosuppression
Hematology
Immunotherapy
Chimeric antigen receptor
medicine.anatomical_structure
nervous system
Oncology
Hematologic Neoplasms
030220 oncology & carcinogenesis
Cancer research
Neoplasm Recurrence, Local
business
030215 immunology
Subjects
Details
- ISSN :
- 10292403 and 10428194
- Volume :
- 62
- Database :
- OpenAIRE
- Journal :
- Leukemia & Lymphoma
- Accession number :
- edsair.doi.dedup.....6e45b55684fba31854336302bde9ee03