PHASE I Clinical Trial:
Detection of anti melanoma specific T cells in PBMC of melanoma patients treated with autologous dendritic cells loaded with tumor cell lysates.
Dendritic cells (DCs)-based therapy has proven to be effective in patients with malignant lymphoma, melanoma, renal and prostate carcinoma. The objectives of this study were to assess the toxicity and immunological response induced by intradermally (i.d) administration of melanoma lysate-pulsed DCs in a clinical phase I trial. Thirteen patients with Stage III or IV malignant melanoma were vaccinated i.d. four times with 3.5 to 15 x 106 DCs/dose once every 10 days. Each vaccine was composed of a mixture of autologous DCs pulsed with tumor lysate from three allogeneic melanoma cell lines in the presence of KLH as adjuvant. DCs derived from peripheral blood mononuclear cells (PBMCs) were morphologic, phenotypic, and functionally characterized in vitro. PBMC harvested before the treatment, one week after each vaccination and one month after the last immunization, were analyzed using ELISPOT.
Twelve patients received all four vaccines and were examined for toxicity and/or immunological responses. There were no grade III or IV toxicities associated with the vaccines or evidence of autoimmunity. After vaccination, 7 of 12 tested patients showed an increased IFN-g production by PBMC in response to allogeneic melanoma cell lines but not to non-melanoma tumor controls. Four of five HLA-A2+ PBMC from patients with anti melanoma activity also showed specific responses against peptides derived from melanoma associated antigens. In vivo, DTH reactions against melanoma cell lysate were observed in 7 of 12 tested patients. In four patients, the disease remained stable for more than 20 months, while the disease progressed in 8 patients. No vitiligo was observed. This study may be one of the first experiences in Latin America using DC based vaccines for the treatment of cancer. More patients and additional studies are necessary to improve tumor rejection response.