The immunogenicity of dendritic cell-based vaccines is not hampered by doxorubicin and melphalan administration.
Immunization of cancer patients is most effective in tumor-free conditions or in the presence of minimal residual disease. In the attempt to develop new strategies able to control tumor recurrence while allowing the development of protective immunity, we have investigated the immunogenic potential of two distinct vaccine formulations when provided alone or upon single and repeated treatment with chemotherapeutics drugs. Vaccine-induced T cell responses were first investigated by tracing Ag-specific T cell responses in mice bearing detectable frequencies of Ag-specific TCR transgenic CD4 and CD8 T cells. These studies indicated that immunization with peptide-pulsed dendritic cells and soluble Ag plus adjuvant elicited a comparable expansion and differentiation of CD4 and CD8 effector cells in the peripheral lymphoid tissues when provided alone or shortly after Doxorubicin or Melphalan administration. We also analyzed the potency of the combined vaccination in transgenic adenocarcinoma mouse prostate mice, which develop spontaneous prostate cancer. Dendritic cell-based vaccination elicited potent tumor-specific cytotoxic responses in mice bearing prostate intraepithelial neoplasia both in the absence and in the presence of Doxorubicin. Together our results indicate that Doxorubicin- or Melphalan-based chemotherapy and Ag-specific vaccination can be combined for adjuvant treatments of cancer patients.
Casati
Anna
A
Cancer Immunotherapy and Gene Therapy Program, San Raffaele Scientific Institute, DIBIT, Milan, Italy.
Zimmermann
Valérie S
VS
Benigni
Fabio
F
Bertilaccio
Maria T S
MT
Bellone
Matteo
M
Mondino
Anna
A
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000633:toxicity; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D018655:Lymphocyte Count; D008558:Melphalan / Q000008:administration & dosage* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology / Q000628:therapy; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics
D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D019496:Cancer Vaccines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004317:Doxorubicin; D008558:Melphalan