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

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

DOI: 10.1158/1078-0432.CCR-16-1860

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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University of Melbourne Researchers

Phillip Darcy Author The Sir Peter Maccallum Department of Oncology

Clare Slaney Author The Sir Peter Maccallum Department of Oncology

Paul Neeson Author The Sir Peter Maccallum Department of Oncology

Ricky Johnstone Author The Sir Peter Maccallum Department of Oncology

Paul Beavis Author The Sir Peter Maccallum Department of Oncology

Related Projects (2)

ATTACKING CANCER USING A UNIFIED IMMUNE SYSTEM

ADOPTIVE CELL TRANSFER INCORPORATING VACCINATION (ACTIV) THERAPY FOR CANCER

We have made a breakthrough in a new treatment for cancer that can destroy large tumours in mice. The treatment involves a transfusion of wh..

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.