Phase I trial of @entity6474 antisense @entity2841 gene-modified XXXX cell (TAG) vaccine.

@entity1 @entity137 @entity66 @entity5 @entity6474 @entity2841 @entity320
PURPOSE: On the basis of the hypothesis that the combined expression of immunostimulatory @entity2841 ( @entity2841 ) and antitumor suppressor @entity6474 antisense (AS) transgenes can break tolerance and stimulate immune responses to @entity5 -associated antigens, we constructed an expression plasmid [the @entity5 -associated glycoprotein (TAG) plasmid] that coexpresses @entity2841 and @entity6474 AS nucleotide sequences and which was incorporated into an autologous whole-cell vaccine. EXPERIMENTAL DESIGN: @entity1 undergoing resection were enrolled. Freshly harvested @entity5 cells were mechanically and enzymatically disaggregated, then electroporated with the TAG vector. The resulting vaccine was irradiated, then aliquoted and cryopreserved until the time of injection. @entity1 received a minimum of 5 to a maximum of 12 monthly intradermal injections. Immune function was monitored at baseline and at months 3 and 6. RESULTS: Vaccine manufacturing efficiency was 84% (32/38). Twenty-three @entity1 received at least 1 vaccination. There were no grade 3 or 4 @entity137 , and grade 1 and 2 events were local in nature. Seventeen of 21 @entity1 had @entity66 ( @entity66 ) at month 2 or later as their best response, and 1 @entity1 with stage IVa malignant @entity320 achieved a complete response (CR) following 11 vaccinations and remains without evidence of disease 2 years following initiation of therapy. Six of 13 @entity1 displayed a positive enzyme-linked immunospot (ELISPOT) response to autologous TAG vaccine at week 12 including 3 @entity1 with prolonged @entity66 or CR. The 3 other @entity1 survived through week 24, as compared with none of the 7 ELISPOT-negative @entity1 . CONCLUSIONS: On the basis of safety and clinical and immunologic results, further evaluation of bifunctional vaccines is warranted.
