Toth, Gabor and Szollosi, Janos and Abken, Hinrich and Vereb, Gyorgy and Szoor, Arpad (2020) A Small Number of HER2 Redirected CAR T Cells Significantly Improves Immune Response of Adoptively Transferred Mouse Lymphocytes against Human Breast Cancer Xenografts. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21 (3): 1039. ISSN , 1422-0067
Full text not available from this repository. (Request a copy)Abstract
HER2 positive JIMT-1 breast tumors are resistant to trastuzumab treatment in vitro and develop resistance to trastuzumab in vivo in SCID mice. We explored whether these resistant tumors could still be eliminated by T cells redirected by a second-generation chimeric antigen receptor (CAR) containing a CD28 costimulatory domain and targeting HER2 with a trastuzumab-derived scFv. In vitro, T cells engineered with this HER2 specific CAR recognized HER2 positive target cells as judged by cytokine production and cytolytic activity. In vivo, the administration of trastuzumab twice weekly had no effect on the growth of JIMT-1 xenografts in SCID mice. At the same time, a single dose of 2.5 million T cells from congenic mice exhibited a moderate xenoimmune response and even stable disease in some cases. In contrast, when the same dose contained 7% (175,000) CAR T cells, complete remission was achieved in 57 days. Even a reduced dose of 250,000 T cells, including only 17,500 CAR T cells, yielded complete remission, although it needed nearly twice the time. We conclude that even a small number of CAR T lymphocytes can evoke a robust anti-tumor response against an antibody resistant xenograft by focusing the activity of xenogenic T cells. This observation may have significance for optimizing the dose of CAR T cells in the therapy of solid tumors.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRASTUZUMAB RESISTANCE; HERCEPTIN-RESISTANT; MONOCLONAL-ANTIBODY; IMMUNOTHERAPY; AMPLIFICATION; EFFICACY; THERAPY; GROWTH; JIMT-1; ERBB2; breast cancer; trastuzumab; chimeric antigen receptor; immunotherapy; cell therapy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Mar 2021 12:25 |
| Last Modified: | 30 Mar 2021 12:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45169 |
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