Hombach, Andreas A. and Rappl, Gunter and Abken, Hinrich (2019) Blocking CD30 on T Cells by a Dual Specific CAR for CD30 and Colon Cancer Antigens Improves the CAR T Cell Response against CD30(-) Tumors. MOLECULAR THERAPY, 27 (10). pp. 1825-1835. ISSN 1525-0016, 1525-0024
Full text not available from this repository. (Request a copy)Abstract
Chimeric antigen receptor (CAR)-engineered T cells are efficacious in controlling advanced leukemia and lymphoma, however, they fail in the treatment of solid cancer, which is thought to be due to insufficient T cell activation. We revealed that the immune response of CAR T cells with specificity for carcinoembryonic antigen (CEA) was more efficacious against CEA(+) cancer cells when simultaneously incubated with an anti-CD30 immunotoxin or anti-CD30 CAR T cells, although the targeted cancer cells lack CD30. The same effect was achieved when the anti-CD30 single-chain variable fragment (scFv) was integrated into the extracellular domain of the anti-CEA CAR. Improvement in T cell activation was due to interfering with the T cell CD30-CD30L interaction by the antagonistic anti-CD30 scFv HRS3; an agonistic anti-CD30 scFv or targeting the high-affinity interleukin-2 (IL-2) receptor was not effective. T cells with the anti-CD30/CEA CAR showed superior immunity against established CEA(+) CD30(-) tumors in a mouse model. The concept is broadly applicable since anti-CD30/TAG72 CAR T cells also showed improved elimination of TAG72(+) CD30(-) cancer cells. Taken together, targeting CD30 on CAR T cells by the HRS3 scFv within the anti-tumor CAR improves the redirected immune response against solid tumors.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANTIIDIOTYPE VACCINE; HODGKINS LYMPHOMA; SPACER DOMAIN; B-CELL; EXPRESSION; RECEPTOR; ACTIVATION; IL-4; PROLIFERATION; CONSTRUCTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Mar 2020 13:43 |
| Last Modified: | 25 Mar 2020 13:43 |
| URI: | https://pred.uni-regensburg.de/id/eprint/26031 |
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