Tumor–dendritic cell fusion as a basis for cancer immunotherapy

Abstract

Problem: Patients with advanced head and neck cancer are at risk for metastasis - local and regional recurrence. One approach to addressing these issues is immunotherapy. Recent studies have identified the dendritic cell (DC) as a critical component in eliciting a T-cell response against neoplastic cells. One immunotherapy approach is fusion of DCs with irradiated tumor cells by electrofusion. Methods: Fusion cells were created using electrofusion technique. We used 2 allogeneic murine tumor lines (D5 and 4T1) virally transduced to express the antigen B-galactosidase. Using beta-galactosidase as a surrogate tumor marker, we crossed immunized mice with irradiated tumor or fusion cells with subsequent tumor challenge intradermally. Fusion cells were also used in the treatment of three-day established pulmonary metastasis. Results: Cross immunization was achieved with irradiated allogenic tumor cells sharing a common antigen given subcutaneously and intranodally. Successful electrofusion of DC and tumor cells was confirmed using fluorescent activated cell sorting (FACS) and cytospin. Significant responses were demonstrated in immunized mice against tumor challenge and established 3-day pulmonary metastasis with syngeneic-fusion cells. Conclusion: Allogeneic tumors sharing a common tumor antigen can immunize against syngeneic tumor challenge. The use of syngeneic tumor-DC fusion cells demonstrated successful immunization against tumor challenge. Fusion cells also resulted in regression of 3-day established pulmonary metastasis. Significance: Difficulties are encountered in successfully and reliably generating tumor cell lines from individual patients, especially in head and neck cancer patients. Findings over recent years suggest that many tumors of the same histological origin but from different individuals may express common antigens. Therefore, a tumor from a different individual (allogeneic) may be feasible for use as a source of antigens. These preclinical studies provide evidence that an allogeneic tumor-dendritic cell fusion vaccine may be a valid approach for head and neck cancer immunotherapy. Support: American Academy of Otolaryngology-Head and Neck Surgery Resident Research Award