UNASSIGNED: 2620 Background: The hyperacute immune response in @entity1 is a potent mechanism of xenograft rejection mediated by complement-fixing natural antibodies recognizing a(1,3)Galactosyl epitopes (aGal) not present on @entity1 cells. We exploited this immune mechanism to create a whole cell cancer vaccine to treat @entity320 . METHODS: Transduction of @entity6844 cells with a retrovirus carrying the a(1,3)Galactosyltransferase gene ( @entity2178 ) yielded B16aGal cells. Transduction with a retrovirus carrying the gene for neomycin gave B16NeoR cells. Whole cell vaccines were prepared by y-irradiation (200 Gy). RESULTS: @entity6844 vaccine expressing aGal epitopes (B16aGal) effectively treated pre-established @entity2 in the a(1,3)Galactosyltransferase knockout @entity19 model, while control @entity6844 vaccines had no effect. Vaccination with B16aGal induced strong long-lasting cell-mediated anti- @entity5 immunity extended to aGal-negative @entity6844 . This was demonstrated by specific in vitro recognition of B16 cells, and successful adoptive transfer of immunity to recipient @entity19 bearing lung @entity320 @entity3 . CONCLUSIONS: This study unequivocally establishes for first time the efficacy of whole cell vaccines expressing aGal epitopes against poorly immunogenic, preestablished @entity320 . These data formed the basis for the initiation of this therapeutic strategy in @entity1 clinical trial currently underway. [Table: see text].

Treatment of pre-established subcutaneous @entity5 and XXXX with a novel vaccine expressing a(1,3)Galactosyl Xenoepitopes.

@entity1 :: ('9606', 'Species') :: ['humans', 'human'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity2178 :: ('183', 'Gene') :: ['aGT'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity2 :: ('MESH:D008175', 'Disease') :: ['subcutaneous and pulmonary B16 tumors'] @entity6844 :: ('MESH:D008546', 'Disease') :: ['B16 melanoma'] @entity3 :: ('MESH:D009362', 'Disease') :: ['metastasis'] @entity320 :: ('MESH:D008545', 'Disease') :: ['melanoma', 'melanoma tumors']
@entity320 :: (MESH:D008545,Disease) :: ['pulmonary melanoma metastasis']
