Journal
ONCOIMMUNOLOGY
Volume 7, Issue 1, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2017.1368604
Keywords
Chimeric antigen receptor; CAR; adoptive cell therapy; tag-CAR; cancer immunotherapy; synthetic biology
Categories
Funding
- National Institutes of Health [R35 CA210039]
- Undergraduate Research Office of Carnegie Mellon University
- American Cancer Society [PF LIB 125429]
- NIH [1S10OD011925-01]
- NATIONAL CANCER INSTITUTE [R35CA210039] Funding Source: NIH RePORTER
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Chimeric antigen receptor T cells (CAR-Ts) are promising cancer therapeutics. However, since cancer cells can lose the CAR-targeted antigen and avoid destruction, targeting multiple antigens with multiple CARs has been proposed. We illustrate here a less cumbersome alternative, anti-tag CARs (AT-CARs) that bind to tags on tumor-targeting antibodies. We have created novel AT-CARs, using the affinity-enhanced monomeric streptavidin 2 (mSA2) biotin-binding domain that when expressed on T cells can target cancer cells coated with biotinylated antibodies. Human T cells expressing mSA2 CARs with CD28-CD3 xi and 4-1BB-CD3 xi signaling domains were activated by plate-immobilized biotin and by tumor cells coated with biotinylated antibodies against the tumor-associated antigens CD19 and CD20. Furthermore, mSA2 CAR T cells were capable of mediating cancer cell lysis and IFN gamma production in an antibody dose-dependent manner. The mSA2 CAR is a universal AT-CAR that can be combined with biotinylated tumor-specific antibodies to potentially target many different tumor types.
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