Chemo-immunotherapy of breast cancer using vesiculated alpha-tocopheryl succinate in combination with dendritic cell vaccination.
In this study, we evaluated the efficacy of vesiculated alpha-tocopheryl succinate (Valpha-TOS) in combination with non-antigen pulsed, nonmatured dendritic cells (nmDC) to treat pre-established tumors of the highly metastatic murine mammary cancer cell line 4T1. We demonstrated that Valpha-TOS in combination with non-antigen pulsed nmDC significantly inhibits the growth of established tumors in vivo and prolongs survival of treated mice. In addition, when initiated after resection of the established primary tumor, the combination treatment dramatically inhibits residual metastatic disease. The clinical response achieved with the combination therapy was correlated with increased interferon-gamma and interleukin-4 (IL-4) production by splenic lymphocytes and draining lymph node cells. Interestingly, when used in combination with Valpha-TOS, nmDC were as effective as tumor necrosis factor-alpha matured DC at inhibiting the growth of pre-established tumors. Valpha-TOS-induced cellular factors collected by high-speed centrifugation of supernatant from Valpha-TOS-treated tumor cells caused maturation of DC as evidenced by the up-regulation of co-stimulatory molecules and secretion of IL-12p70. These results demonstrate the potential usefulness of Valpha-TOS + DC chemo-immunotherapy in treating established primary mammary tumors as well as residual metastatic disease.
Department of Microbiology and Immunology, University of Arizona, Tucson, AZ 85724, USA.
Lalitha V
LV
Ramanathapuram
Tobias
T
Hahn
Sharon M
SM
Dial
Emmanuel T
ET
Akporiaye
D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology*; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006360:Heat-Shock Proteins; D007167:Immunotherapy; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; D014810:Vitamin E; D024505:Tocopherols