ABSTRACT
BACKGROUND/AIM: Dendritic cell-based vaccine therapy for renal cell carcinoma is effective but requires improvement. Here we explored whether combination therapy with dendritic cell-based vaccine and anti-CD69 antibody can enhance antitumor efficacy in renal cell carcinoma-bearing mice. MATERIALS AND METHODS: Balb/c mice were challenged subcutaneously with murine renal cell carcinoma (Renca) cells. On day 3 after tumor cell inoculation, tumor-bearing mice either were left untreated or were treated with Renca tumor lysate-pulsed dendritic cells (i.e. dendritic cell-based vaccine), anti-CD69 antibody, or a combination of Renca tumor lysate-pulsed dendritic cells with anti-CD69 antibody. The mice were sacrificed on day 28. Tumor volume was measured for analysis of antitumor efficacy. Spleens were excised to evaluate antitumor immunological responses by measuring the proliferation and activation of T cells, which have the capacity to recognize and destroy tumor cells. RESULTS: Combination treatment with Renca tumor lysate-pulsed dendritic cells and anti-CD69 antibody resulted in significant decreases in tumor volume and significant increases in T-cell proliferation and activity, compared with no treatment or either treatment alone. CONCLUSION: These findings indicate that anti-CD69 antibody can potentiate antitumor efficacy of dendritic cell-based vaccine. The augmented therapeutic efficacy conferred by the combination therapy may be associated with increased T-cell proliferation and activity.
Subject(s)
Antigens, CD/metabolism , Antigens, Differentiation, T-Lymphocyte/metabolism , Antineoplastic Agents , Cancer Vaccines , Carcinoma, Renal Cell , Dendritic Cells , Kidney Neoplasms , Lectins, C-Type/metabolism , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacology , Antigens, CD/immunology , Antigens, Differentiation, T-Lymphocyte/immunology , Antineoplastic Agents/immunology , Antineoplastic Agents/pharmacology , Cancer Vaccines/immunology , Cancer Vaccines/pharmacology , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/therapy , Cell Proliferation/drug effects , Cell- and Tissue-Based Therapy , Combined Modality Therapy , Dendritic Cells/immunology , Dendritic Cells/transplantation , Disease Models, Animal , Kidney/cytology , Kidney/drug effects , Kidney Neoplasms/immunology , Kidney Neoplasms/therapy , Lectins, C-Type/immunology , Mice , Mice, Inbred BALB C , T-Lymphocytes, Cytotoxic/immunologyABSTRACT
In the current study, we investigated whether anti-CD27 monoclonal antibody can enhance the antitumor efficacy of a dendritic cell-based vaccine in prostate cancer-bearing mice. The overall therapeutic effect of a dendritic cell-based vaccine for prostate cancer remains moderate. A prostate cancer model was established by subcutaneous injection of RM-1 tumor cells into male C57BL/6 mice on day 0. After 4 days, tumor-bearing mice were treated with RM-1 tumor lysate-pulsed dendritic cells (i.e., dendritic cell-based vaccine), anti-CD27 monoclonal antibody, or a combination of RM-1 tumor lysate-pulsed dendritic cells with anti-CD27 monoclonal antibody. Mice were killed at 21 days after tumor cell implantation. Tumor size was measured for assessment of antitumor effect. Spleens were collected for analysis of antitumor immune responses. The antitumor immune responses were evaluated by measuring the proliferation and activity of T cells, which have the ability to kill tumor cells. The combination therapy with RM-1 tumor lysate-pulsed dendritic cells and anti-CD27 antibody significantly enhanced T-cell proliferation and activity, and significantly reduced tumor growth, compared with monotherapy with RM-1 tumor lysate-pulsed dendritic cells or anti-CD27 antibody. Our results suggest that combined treatment can strengthen antitumor efficacy by improving T-cell proliferation and activity.
