Medical & Clinical Research

Author(s): Chandan R Bora, Ileana Nordet Carrera, Fidel S Rampersad , Andrea M Richardson and Pramod S Dhembare*

Background and Aims: Dendritic cell (DC)-based immunotherapy is promising as a viable tool in cancer treatment. Dendritic cell (DC)-based vaccination can provoke antitumor T cell responses in vivo. These case studies examined feasibility and outcome of DC-based tumor vaccination for patients with advanced cancers. This approach has been used mostly in patients in the presence of defined tumor antigens.

Experimental Design: Accessible tumor tissue was disrupted into single cell suspensions. Autologous DCs were prepared from adherent peripheral blood mononuclear cells and cultured in granulocyte macrophage colony-stimulating factor, interleukin and autologous plasma. Tumor cells and DCs were co-cultured in the presence of polyethylene glycol to generate the fusions. Fusion cells were quantified by determining the percentage of cells that co-express tumor and DC markers. Patients were vaccinated with three doses of DC (10 X 106 ) were administered after every 2 weeks’ intervals and assessed weekly for toxicity, and tumor response was assessed at 3 months after completion of vaccination.

Results: Vaccination was well tolerated. No physical signs of autoimmunity were detected. There was no evidence of significant toxicity from vaccine or adjuvant. There was increased expression of T helper type 1 cytokines. Vaccination resulted in a significant reduction in the level of prostate-specific antigen (PSA) in the prostate cancer patient. Disease was stable upto 6 months in cases of breast and cervical cancer patients.

Conclusion: DC-based vaccination can stimulate an antitumoral T cell response in patients with various cancers. This data indicates that vaccination with autologous tumor-pulsed DCs generated from peripheral blood is safe and can induce tumorspecific cellular cytotoxicity. Clinical responses are achievable, even in patients with advanced disease.