UICC World Cancer Congress 2006

Objective:Cervical cancer is the leading cause of cancer related deaths among Indian women, with human papilloma virus playing a crucial role. Majority of women infected with HPV, clear the infection. Only a small minority with persistent HPV infection show progression of lesion, from low grade CIN to invasive cancer. Tumor cells have been shown to evade the immune system by down-regulating their Class I MHC molecules. Studies using mature dendritic cells have shown that it is possible to induce immune response to various tumors.

Methods:Peripheral blood monocytes of patients were cultured in the presence of IL-4&GM-CSF for 7 days. These immature dendritic cells (DCs) were then primed with autologous tumor lysates and allowed to mature in the presence of TNF-alpha and IL-1beta for 2-3 days. These DCs were characterized for phenotypic markers: HLA DP, DQ, DR, CD86, and CD14 by FACS analysis. Proliferation assays were done to characterize the functions of mature DCs. The study is an ongoing, randomized phase one clinical trial. So far 9 patients have been included in the trial.

Results:Phenotypic characterization showed that mature tumor-specific dendritic cells of the patients were all – HLA DP, DQ, DR (+++), CD86 (+++), CD14 (-). Proliferation assays indicate that priming can make the mature dendritic cells efficient in presenting antigens to autologous lymphocytes by inducing a strong proliferation response in these cells. 9 patients have completed vaccination, DTH response was observed in 3/9 patients. An objective tumour response not been observed yet. Minimal or no toxicity was observed in the patients so far.