Comparative studies of a retrovirus versus a poxvirus vector in whole tumor-cell vaccines

A number of experimental and clinical studies have used retroviral vectors to express transgenes in whole tumor-cell vaccines. Recently, poxvirus vect ors such as vaccinia or avipox have been used toward this goal. The studies reported here compare for the first time the use of a retroviral vector ve rsus a poxvirus vector (vaccinia) in whale tumor-cell vaccines, The transge ne used was the T-cell costimulatory molecule B7-1, and the tumor was the w eakly or noninmunogenic MC38 murine colon adenocarcinoma. Recombinant retro virus (R-B7) and the recombinant vaccinia (V-B7) induced equivalent express ion of B7 on the surface of the carcinoma cell. Using live whole-tumor cell as as vaccine, cells transduced via recombinant retrovirus (MC38/R-B7) and recombinant vaccinia (MC38/V-B7) equally induced protection against challe nge by native MC38 cells 14 days later. Upon rechallenge with native MC38 c ells 40 days later, however, the MC38/R-B7 vaccine was shown to be less eff ective than the MC38/V-B7 vaccine. Similar results were obtained when the t umor cells were irradiated prior to administration. When comparative studie s were conducted in which X-irradiated tumor-cell vaccines were given to mi ce bearing experimental lung metastases, the MC38/V-B7 vaccine was shown to be significantly (P = 0.0351) more effective than the MC38/R-B7 vaccine. A dditional studies were carried out in mice that had received vaccinia virus previously. Again, the X-irradiated MC38/V-B7 vaccine was statistically (P = 0.024) more effective than the MC38/R-B7 vaccine in the elimination of m etastases. When the naive and vaccinia-immune mice for each vaccination gro up were combined for meta-analysis (n = 16), the MC38/V-B7 was significantl y more effective than the MC38/ R-B7 in the treatment of pulmonary metastas es (P = 0.0014) in this model. These studies thus demonstrate for the first time that a whole tumor-cell vaccine (either live or X-irradiated) contain ing a vaccinia transgene is at least as efficient, and sometimes more effic ient, in inducing antitumor effects compared with the same vaccine using a retrovirus to express the transgene. The implications for the clinical appl ications of such approaches are discussed.