Improvement of dendritic cell based therapeutic cancer vaccine with components of Toxoplasma gondii

Clin Vaccine Immunol. 2009 Aug 5. [Epub ahead of print]

Improvement of dendritic cell based therapeutic cancer vaccine with components of Toxoplasma gondii

Motamedi M, Arab S, Moazzeni SM, Khamis Abadi M, Hadjati J.

Lorestan University of Medical Sciences, Khoramabad, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, Tarbiat Modarres University, Tehran, Iran.

The use of Dendritic cells (DCs) as a cellular adjuvant is a promising approach in immunotherapy of cancer. It has been previously demonstrated that dendritic cells (DCs) pulsed ex vivo with Toxoplasma gondii antigens trigger a systemic Th1-biased specific immune response and induce a protective and specific anti-toxoplasma immunity. In the present study, we demonstrate that tumor antigen pulsed DCs matured in the presence of Toxoplasma gondii components induce a potent anti-tumor response in a mouse model of fibrosarcoma. Bone-marrow derived DCs (BMDCs) were cultured in the presence of GM-CSF and IL-4. After 5 days, tumor lysates with/without T. gondii lysate were added to the culture for another 2 days. Cytokine production in BMDC culture and co culture supernatant of DC and splenic cells was evaluated. For immunization, 7 days after tumor challenge, different groups of Balb/c mice received different kinds of dendritic cells subcutaneously (S.C.) around the tumor site. Tumor growth was monitored and two weeks after DC immunotherapy cytotoxic activity and infiltration of CD8+ T cell monitored in different groups. According to the findings immunotherapy with T.gondii matured dendritic cells led to a significant increase in activity of cytotoxic T cells and decreased tumor growth of immunized animals. Immature DCs didn't cause any change in cytotoxic activity and tumor growth rate compare to normal or controls. The current study suggests that specific anti-tumor immune response can be induced by DCs matured with T.gondii component and provide the basis for the use of T.gondii in DC-targeted clinical therapies.

PMID: 19656994 [PubMed - as supplied by publisher]