Immunotherapy of established murine squamous cell carcinoma using fused dendritic-tumor cell hybrids.
OBJECTIVE: To investigate the therapeutic efficacy of fused dendritic-tumor cell hybrids against murine squamous cell carcinoma (SCC). DESIGN: Squamous cell carcinoma VII is a poorly immunogenic murine SCC tumor in C3H/HEN (H-2(K)) mice. Subdermal tumors were established by inoculation in the mid abdomen of mice. Tumor diameters were measured with a Vernier caliper and used as an indication of treatment efficacy. Survival studies were performed on mice with 3-day pulmonary metastasis or subdermal tumors. Dendritic cells were generated from bone marrow and cultured for 8 days. Dendritic cells were harvested and mixed with cultured tumor cells in a 1:1 ratio. Cell fusion was achieved by exposing the cell mixture to an alternate electrical current to bring cells into alignment and close together, followed by a short direct electrical current pulse. SUBJECTS: Female C3H/HEN mice aged 8 to 12 weeks. INTERVENTIONS: Mice with 3-day established SCCVII tumors were vaccinated by inguinal intranodal injection of fusion cells (0.3 x 10(6) per side). To support the development of antitumor immunity, mice were given adjuvant injections intraperitoneally. Anti-OX40R monoclonal antibodies or interleukin 12 were used. Treatment groups included no treatment, anti-OX40R monoclonal antibodies or adjuvant IL-12 alone, fusion cells alone, and fusion cells with adjuvant treatment. MAIN OUTCOME MEASURES: Tumor size and overall survival. RESULTS: Mice treated with adjuvant treatment or fusion cells alone did not show a statistical difference in tumor growth when compared with controls. In contrast, fusion cells with adjuvant treatment demonstrated a significant decrease in tumor size when compared with nontreated mice (P < .001). Treatment with fusion cells also resulted in increased survival in the pulmonary metastasis and subdermal tumor models. CONCLUSION: Immunotherapy with fused dendritic-tumor cell hybrids can significantly affect 3-day established sSCC VII tumor growth.
Lee, WT; Tamai, H; Cohen, P; Teker, AM; Shu, S
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