Dr. Daniel Gillet Profile

Dr. Daniel Gillet

at CEA Saclay

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Proceedings Article | 4 June 2002 Paper

Novel cancer vaccines prepared by anchoring cytokines to tumor cells avoiding gene transfection

Philippe Nizard, David-Alexandre Gross, Alexandre Chenal, Bruno Beaumelle, Konstadinos Kosmatopoulos, Daniel Gillet

Proceedings Volume 4625, (2002) https://doi.org/10.1117/12.469781

KEYWORDS: Tumors, Proteins, Cancer, Melanoma, Molecules, Lymphoma, Oncology, Receptors, Viruses, Safety

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Cytokines have a strong potential for triggering anticancer immunity if released in the tumor microenvironment. Successful vaccines have been engineered using tumor cells genetically modified to secrete the cytokines. Unfortunately, this approach remains difficult and hazardous to perform in the clinic. We describe a new way of combining cytokines with tumor cells to prepare anticancer vaccines. This consists in anchoring recombinant cytokines to the membrane of killed tumor cells. Attachment is mediated by a fragment of diphtheria toxin (T) genetically connected to the cytokine. It is triggered by an acid pH pulse. The method was applied to IL-2, a potent anti-tumor cytokine. IL-2 anchored to the surface of tumor cells by the T anchor retained its IL-2 activity and remained exposed several days. Interestingly, vaccination of mice with these modified tumor cells induced a protective anti-tumor immunity mediated by tumor-specific cytotoxic T lymphocytes. This procedure presents several advantages as compared to the conventional approaches based on the transfection of tumor cells with cytokine genes. It does not require the culture of tumor cells from the patients and eliminates the safety problems connected with viral vectors while allowing the control of the amount of cytokines delivered with the vaccine.

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