Journal article

Dual-specific Chimeric Antigen Receptor T Cells and an Indirect Vaccine Eradicate a Variety of Large Solid Tumors in an Immunocompetent, Self-antigen Setting

Clare Y Slaney, Bianca von Scheidt, Alexander J Davenport, Paul A Beavis, Jennifer A Westwood, Sherly Mardiana, David C Tscharke, Sarah Ellis, H Miles Prince, Joseph A Trapani, Ricky W Johnstone, Mark J Smyth, Michele W Teng, Aesha Ali, Zhiya Yu, Steven A Rosenberg, Nicholas P Restifo, Paul Neeson, Phillip K Darcy, Michael H Kershaw

CLINICAL CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2017

Abstract

Purpose: While adoptive transfer of T cells bearing a chimeric antigen receptor (CAR) can eliminate substantial burdens of some leukemias, the ultimate challenge remains the eradication of large solid tumors for most cancers. We aimed to develop an immunotherapy approach effective against large tumors in an immunocompetent, self-antigen preclinical mouse model.Experimental Design: In this study, we generated dual-specific T cells expressing both a CAR specific for Her2 and a TCR specific for the melanocyte protein (gp100). We used a regimen of adoptive cell transfer incorporating vaccination (ACTIV), with recombinant vaccinia virus expressing gp100, to treat a range of tumors including ortho..

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Grants

Awarded by Cancer Council of Victoria, Australia


Awarded by National Health and Medical Research Council (NHMRC) of Australia


Awarded by National Breast Cancer Foundation


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

This work was supported by grants from the Cancer Council of Victoria, Australia (1066554), The Peter MacCallum Cancer Center Foundation, and the National Health and Medical Research Council (NHMRC) of Australia (1103352). C.Y. Slaney and P. Beavis were supported by Postdoctoral Fellowships from the National Breast Cancer Foundation of Australia. A.J. Davenport and S. Mardiana received Postgraduate Scholarships from the Fight Cancer Foundation and University of Melbourne respectively. R.W. Johnstone and M.J. Smyth were supported by Senior Principal Research Fellowships from the NHMRC. M.H. Kershaw and P.K. Darcy were supported by Senior Research Fellowships from the NHMRC. S. Ellis was supported by a New Investigator Grant from the NHMRC.