Journal
ADVANCED SCIENCE
Volume 8, Issue 6, Pages -Publisher
WILEY
DOI: 10.1002/advs.202003091
Keywords
CD38; chimeric antigen receptor; combinatorial antibody library; tumor-associated antigen
Categories
Funding
- National Natural Science Foundation of China [31500632, U19A2011]
- Science and Technology Commission of Shanghai Municipality [16DZ1910200]
- JPB Foundation [1097]
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A novel approach using CAR-T cells with an avidity-based selection method has been proposed by scientists, achieving specific recognition of tumor cells with reduced off-tumor effects and retained antitumor efficacy.
Using T-cell chimeric antigen receptors (CAR-T) to activate and redirect T cells to tumors expressing the cognate antigen represents a powerful approach in cancer therapy. However, normal tissues with low expression of tumor-associated antigens (TAAs) can be mistargeted, resulting in severe side effects. An approach using a collection of T cells expressing a diverse, 10(6)-member combinatorial cellular library of CARs, in which members can be specifically enriched based on avidity for cell membrane antigens, is reported. Using CD38 as the target antigen, an efficient and effective selection of CARs specifically recognizing CD38(+) tumor cells is demonstrated. These selected CAR-T's produce cytokines known to be associated with T cell activation in a CD38 expression-dependent manner. This avidity-based selection endows the engineered T cells with minimal off-tumor effects, while retaining robust antitumor efficacy both in vitro and in vivo. The described method may facilitate the application of CAR-T therapy to TAAs previously considered undruggable.
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