Dendritic cells pulsed with tumor-derived lysate augment t cell mediated tumor cell lysis

Abstract

Problem: Immunotherapy of malignant diseases mediated by dendritic cells (DC) pulsed with tumor antigens is a promising new tool in the individual treatment of malignant diseases. Tumor-specific T cells should be generated by coincubation with DC pulsed with tumor-derived lysate (TL), and their cytolytic activity should be assessed in an autologous ex vivo system. Methods: DC were generated from peripheral blood monocytes using standard techniques and pulsed with autologous TL from patients with head and neck squamous cell carcinoma (HNSCC). Pulsed DC are able to induce the generation of cytotoxic T cells (CTL). CTL were then coincubated with autologous tumor cells on a chorioallantois membrane. Tumor cells coincubated with 200μl (0.5 mg/mL) Cisplatin; native T cells or cell culture medium served as controls. Results: Coincubation of HNSCC cells with CTL resulted in a decrease of viable cells at T24 and T48 when compared with the control containing only medium or native T cells. The coincubation of HNSCC with Cisplatin resulted in a decrease of about 50% at T24 and T48. Conclusion: DC pulsed with TL were able to present tumor antigens to lymphocytes resulting in the generation of tumor-specific CTL inducing tumor cell lysis. DC pulsed with TL may represent a method for inducing immune responses against squamous cell carcinomas of the upper aerodigestive tract. Significance: These results are encouraging for the possible application of pulsed DC in the therapy of HNSCC. Support: None reported.