Modified Tumor Cells

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Attempts to increase the immunogenicity of tumor cell vaccines have included the infection of cancer cells with viruses (e.g., vaccinia virus [Arroyo et al. 1990; Bash 1993] and vesicular stomatitis virus [Livingston et al. 1985]) to create oncolysates that contain both viral and tumor antigens. The strong viral antigens act as immu-nologic adjuvants, which enhance immune responses to the tumor antigens.

Transfection of certain genes into tumor cells can also increase their immuno-genicity (Colombo and Forni 1994; Colombo and Rodolfo 1995; Pardoll 1995). Patients have been treated with tumor cells genetically modified ex vivo or in vitro to express different classes of genes, including cytokines, T cell costimulatory molecules, as well as allogeneic or xenogeneic MHC class I molecules.

An alternative to the use of whole tumor cells in vaccines has been the use of relevant and immune-activating portions of tumor cells and removal of portions proven to be irrelevant and immune suppressing. In experimental murine models, partially purified fractions of allogeneic tumor cell lines that shed tumor antigen have been shown to yield preparations capable of stimulating immune responses (Johnston et al. 1994). This method of preparing a tumor vaccine has been used in clinical trials (Bystryn 1993; Bystryn et al. 1992a,b), in combination with adjuvants such as alum or DETOX (Schultz et al. 1995).

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