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Hammill JA, VanSeggelen H, Helsen CW, et al. Designed ankyrin repeat proteins are effective targeting elements for chimeric antigen receptors. J Immunother Cancer. 2015;3:55doi: 10.1186/s40425-015-0099-4.
Hammill, J. A., VanSeggelen, H., Helsen, C. W., Denisova, G. F., Evelegh, C., Tantalo, D. G., Bassett, J. D., & Bramson, J. L. (2015). Designed ankyrin repeat proteins are effective targeting elements for chimeric antigen receptors. Journal for immunotherapy of cancer, 355. https://doi.org/10.1186/s40425-015-0099-4
Hammill, Joanne A, et al. "Designed ankyrin repeat proteins are effective targeting elements for chimeric antigen receptors." Journal for immunotherapy of cancer vol. 3 (2015): 55. doi: https://doi.org/10.1186/s40425-015-0099-4
Hammill JA, VanSeggelen H, Helsen CW, Denisova GF, Evelegh C, Tantalo DG, Bassett JD, Bramson JL. Designed ankyrin repeat proteins are effective targeting elements for chimeric antigen receptors. J Immunother Cancer. 2015 Dec 15;3:55. doi: 10.1186/s40425-015-0099-4. eCollection 2015. PMID: 26673402; PMCID: PMC4678647.
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J Immunother Cancer. 2015 Dec 15;3:55. doi: 10.1186/s40425-015-0099-4. eCollection 2015.

Designed ankyrin repeat proteins are effective targeting elements for chimeric antigen receptors.

Journal for immunotherapy of cancer

Joanne A Hammill, Heather VanSeggelen, Christopher W Helsen, Galina F Denisova, Carole Evelegh, Daniela G M Tantalo, Jennifer D Bassett, Jonathan L Bramson

Affiliations

  1. Department Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON Canada.

PMID: 26673402 PMCID: PMC4678647 DOI: 10.1186/s40425-015-0099-4

Abstract

BACKGROUND: Adoptive cell transfer of tumor-specific T lymphocytes (T cells) is proving to be an effective strategy for treating established tumors in cancer patients. One method of generating these cells is accomplished through engineering bulk T cell populations to express chimeric antigen receptors (CARs), which are specific for tumor antigens. Traditionally, these CARs are targeted against tumor antigens using single-chain antibodies (scFv). Here we describe the use of a designed ankyrin repeat protein (DARPin) as the tumor-antigen targeting domain.

METHODS: We prepared second generation anti-HER2 CARs that were targeted to the tumor antigen by either a DARPin or scFv. The CARs were engineered into human and murine T cells. We then compared the ability of CARs to trigger cytokine production, degranulation and cytotoxicity.

RESULTS: The DARPin CARs displayed reduced surface expression relative to scFv CARs in murine cells but both CARs were expressed equally well on human T cells, suggesting that there may be a processing issue with the murine variants. In both the murine and human systems, the DARPin CARs were found to be highly functional, triggering cytokine and cytotoxic responses that were similar to those triggered by the scFv CARs.

CONCLUSIONS: These findings demonstrate the utility of DARPins as CAR-targeting agents and open up an avenue for the generation of CARs with novel antigen binding attributes.

Keywords: CAR; Cancer; Chimeric antigen receptor; DARPin; Designed ankyrin repeat protein; Immunotherapy

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