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Treatment of Pre-established Subcutaneous Tumors and Pulmonary Melanoma Metastasis With a Novel Vaccine Expressing alpha Galactosyl Xenoepitopes



Treatment of Pre-established Subcutaneous Tumors and Pulmonary Melanoma Metastasis With a Novel Vaccine Expressing alpha Galactosyl Xenoepitopes



FASEB Journal 18(4-5): Abst 85 30



The hyperacute immune response in humans is a potent mechanism of xenograft rejection mediated by complement-fixing natural antibodies that recognize ?(1,3)Galactosyl epitopes ((Gal) not present on human cells. In this study we exploited this immune mechanism to create whole cell cancer vaccines to treat melanoma tumors. We used ?(1,3)Galactosyltransferase ((GT) knockout mice, that do not express ?Gal epitopes on their cell surfaces and develop anti-?Gal antibodies. Vaccination with ?Gal(+).B16 but not with ?Gal(null).B16 melanoma vaccines effectively treated pre-established subcutaneous and pulmonary ?Gal(null).B16 tumors. Anti-tumor immunity induced in ?Gal(+).B16 vaccinated mice was melanoma-specific and extended to ?Gal(null).B16 cells demonstrated by intracellular TNF-? and up-regulation of CD25 and CD69. Vaccination with ?Gal(+).B16 induced cell-mediated immunity adoptively transferred to recipients reducing lung metastases. This study unequivocally establishes for first time the efficacy of (Gal(+).B16 vaccines against these poorly immunogenic, pre-established melanoma models. The sole difference in the glycosylation pattern in this vaccine was sufficient to function as immune-adjuvant and induced strong long-lasting cell-mediated anti-tumor immunity. These data formed the basis for the initiation of this therapeutic strategy in human clinical trials currently underway. Supported by Newlink Genetics Sponsored Research Agreement. .

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Accession: 035980585

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