Vaccination
therapy using dendritic cells (DC) as antigen presenting cells (APC) has shown significant promise in laboratory and animal studies as a potential treatment for malignant diseases. Pulsing of autologous DCs with
tumor-associated
antigens (TAA) is a method often used for
antigen delivery and choice of suitable
antigens plays an important role in designing an effective
vaccine. We identified two
HLA-A2 binding novel 9-mer
peptides of the TAA MUC1, which is overexpressed on various hematological and epithelial
malignancies. Cytotoxic T cells generated after pulsing DC with these
peptides were able to induce lysis of
tumor cells expressing MUC1 in an
antigen-specific and HLA-restricted fashion. Within two clinical studies, we demonstrated that vaccination of patients with advanced
cancer using DCs pulsed with MUC1 derived
peptides is well tolerated without serious side effects and can induce immunological responses. Of 20 patients with metastatic
renal cell carcinoma, 6 patients showed regression of
metastases with 3 objective responses (1 CR, 2 PR). Furthermore, we found that in patients responding to treatment T cell responses for
antigens not used for treatment occurred suggesting that
antigen spreading in vivo might be a possible mechanism of mediating antitumor effects. These results demonstrate that
immunotherapy in patients with advanced
malignancies using autologous DCs pulsed with MUC1 derived
peptides can induce immunological and clinical responses. However, further clinical studies are needed to identify the most potent treatment regimen that can consistently mediate an antitumor immune response in vivo.