Novel approaches for activation and expansion of genetically modified T cells in vivo

Funded Activity Summary

Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engineered in culture with tumor recognition receptors. When transferred into mice, these genetically engineered cells can release toxic and inflammatory proteins that cause tumor destruction. In this proposal we wish to further test this approach in mice by enginneering the mouse killer T cells with (i) receptors that provide stronger signals for killing and proliferation; and (ii) with receptors targeting other structures on tumor cells including the tumor vasculature as a means to overcome tumor escape. In addition, we wish to test a novel approach of combining both genetic engineering and vaccination strategies for expanding gene-modified cells after adoptive transfer. These studies will allow the best receptor genes to be transferred to human white blood cells and examined for anti-tumor effects in immune-deficient mice.

Funded Activity Details

Start Date: 01-01-2002

End Date: 01-01-2002

Funding Scheme: NHMRC Project Grants

Funding Amount: $115,660.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Diagnostic radiography

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

breast cancer | cancer | co-stimulatory molecules | colon cancer | cytotoxic T lymphocytes | gene therapy | murine models | ovarian cancer | retroviral gene transfer | tumour immunotherapy

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