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| Item Type: | Article |
|---|---|
| Title: | Efficacy of CAR T-cell therapy in large tumors relies upon stromal targeting by IFNγ |
| Creators Name: | Textor, A., Listopad, J.J., Wührmann, L.L., Perez, C., Kruschinski, A., Chmielewski, M., Abken, H., Blankenstein, T. and Charo, J. |
| Abstract: | Adoptive T cell therapy using chimeric antigen receptor-modified T cells (CAR-T therapy) has shown dramatic efficacy in patients with circulating lymphoma. However, eradication of solid tumors with CAR-T therapy has not been reported yet to be efficacious. In solid tumors, stroma destruction, due to MHC-restricted cross-presentation of tumor antigens to T cells, may be essential. However, CAR-Ts recognize antigens in an MHC-independent manner on cancer cells but not stroma cells. In this report, we show how CAR-Ts can be engineered to eradicate large established tumors with provision of a suitable CD28 costimulatory signal. In a HER-2-dependent tumor model, tumor rejection by HER-2-specific CAR-Ts was associated with sustained influx and proliferation of the adoptively transferred T cells. Interestingly, tumor rejection did not involve NK cells, but was associated instead with a marked increase in the level of M1 macrophages and a requirement for IFN{gamma} receptor expression on tumor stroma cells. Our results argue that CAR-T therapy is capable of eradicating solid tumors through a combination of antigen-independent stroma destruction and antigen-specific tumor cell targeting. |
| Keywords: | Chimeric Antigen Receptor, Solid Tumor, Adoptive T Cell Therapy, IFN{gamma}, Animals, Mice |
| Source: | Cancer Research |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Volume: | 74 |
| Number: | 23 |
| Page Range: | 6796-6805 |
| Date: | 1 December 2014 |
| Official Publication: | https://doi.org/10.1158/0008-5472.CAN-14-0079 |
| PubMed: | View item in PubMed |
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