Adoptive immunotherapy as an in vivo model to explore antitumor mechanisms induced by a recombinant anticancer vaccine

J Immunother. 1997 Jan;20(1):48-59. doi: 10.1097/00002371-199701000-00005.


We have described previously the construction, generation, and in vivo biologic consequences of a recombinant vaccinia virus containing the human CEA gene (rV-CEA) in an experimental murine colon carcinoma model. Immunization of C57BL/6 mice with rV-CEA led to antigen-specific inhibition of tumor growth in both prophylactic and therapeutic settings. Although such antitumor effects were correlated with the induction of CEA-specific T-cell responses, their exact contribution in the tumor rejection mechanism remained unclear. In this study, we examined the mechanism of action of rV-CEA, with emphasis on definition of the immune cells important for such antitumor effects. To that end, a cellular adoptive transfer model was established in vivo, which allowed specific functional analysis of donor-derived immune cells in naive, sublethally irradiated, tumor-bearing recipients. Splenocytes from rV-CEA-immunized donors expressed strong antitumor activity in such tumor-bearing recipients, whereas nonimmune donor cells did not. Depletion of immune T cells before cellular transfer abolished the antitumor response. Moreover, depletion of CD8+ T cells before transfer resulted in the loss of antitumor activity, despite the presence of CD4+ T cells. In contrast, antitumor activity was demonstrable with CD8-containing, CD4-depleted effectors, although it was not as effective as with both T-cell subpopulations combined. Finally, in beta 2-microglobulin/CD8+ T-cell-deficient mice, rV-CEA immunization exerted only partial antitumor protection, compared with the immune-competent controls. Overall, we demonstrated that (a) antitumor activity induced by rV-CEA was essentially mediated by CD8+ effectors; and (b) the combination of both CD8+ and CD4+ lymphocytes led to maximal antitumor therapeutic effects, suggesting an important helper or immunoregulatory contribution of the CD4+ subset. Thus, adoptive cellular transfer strategies may have implications for both the study of recombinant anticancer vaccines and the development of potential clinical applications for cancer immunotherapy.

MeSH terms

  • Adenocarcinoma / therapy*
  • Animals
  • Antibody Specificity
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / therapeutic use*
  • Carcinoembryonic Antigen / genetics*
  • Cell Division / immunology
  • Colonic Neoplasms / therapy*
  • Disease Models, Animal
  • Humans
  • Immunotherapy, Adoptive*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Recombination, Genetic
  • Spleen / cytology
  • Spleen / immunology
  • Vaccines, Synthetic / therapeutic use*


  • Cancer Vaccines
  • Carcinoembryonic Antigen
  • Vaccines, Synthetic