Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 19, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/ijms19020340
Keywords
adoptive T cell therapy; chimeric antigen receptors; PD-1; immune-checkpoint; cancer immunotherapy; gene editing; gene therapy; CRISPR/Cas9
Funding
- Asan-Minnesota Institute for Innovating Transplantation (AMIT)
- National Research Foundation of Korea (NRF) - Ministry of Science and ICT (MSIT) [NRF-2015K1A4A3046807]
- Corrigan family
- Children's Cancer Research Fund
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL095791] Funding Source: NIH RePORTER
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Chimeric antigen receptor (CAR) T cell therapy represents the first U.S. Food and Drug Administration approved gene therapy and these engineered cells function with unprecedented efficacy in the treatment of refractory CD19 positive hematologic malignancies. CAR translation to solid tumors is also being actively investigated; however, efficacy to date has been variable due to tumor-evolved mechanisms that inhibit local immune cell activity. To bolster the potency of CAR-T cells, modulation of the immunosuppressive tumor microenvironment with immune-checkpoint blockade is a promising strategy. The impact of this approach on hematological malignancies is in its infancy, and in this review we discuss CAR-T cells and their synergy with immune-checkpoint blockade.
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