Naked DNA and Adenoviral Immunizations for Immunotherapy of Prostate Cancer: A Phase I/II Clinical Trial

Immune responses against PSMA after gene-based vaccination for immunotherapy – A: results from immunizations in animals

“…This result is in agreement with earlier observations both in animals and in humans. 4,[37][38][39] The expansion and differentiation of both T and B lymphocytes is affected 36 since the adjuvant effect of GM-CSF influences both cytotoxic T-cell generation ( Figure 2) and antibody development ( Figure 5).…”

“…From an earlier clinical trial, 4 we found that the magnitude of the response could be increased if the plasmid vaccine is coinjected with GM-CSF, a cytokine that has been known for its adjuvant properties. 27 The above experiment was repeated, but this time recombinant rat GM-CSF (9 mg/m 2 ) was added to the immunization cocktail.…”

“…[1][2][3][4] The use of PSArecombinant vaccinia virus has also been found to be safe and lead to an immune response. 5,6 The main effectors in antitumor immunity after DNA immunization are CD8 þ cytotoxic T cells that recognize tumor or tumorassociated antigen-derived peptides expressed in association with MHC class I molecules.…”

DNA Vaccines for Prostate Cancer

“…Mincheff et al conducted a phase I/II trial using a prime-boost strategy with adenovirus and plasmid DNA encoding the extracellular portion of PSMA [52]. The PSMA DNA vaccine was evaluated alone, in combination with a separate vector encoding the costimulatory molecule CD86, or a plasmid encoding both PSMA and CD86.…”

“…Given the complicated trial design, heterogeneous subject population, and primary immunological endpoint (DTH responses at the injection site), interpretation of the trial’s clinical and immunological results remains difficult. Nevertheless, no significant adverse events were observed and DTH responses were detected in more patients when GM-CSF was included as a vaccine adjuvant and in individuals receiving a DNA vaccine encoding CD86 [52, 53]. In separate studies, Slovin, Wolchok and colleagues have investigated DNA vaccines targeting PSMA using a xenoantigen prime-boost approach [54].…”