Exosomes in cancer immunotherapy: preclinical data

Abstract

Tumor cells present tumor antigens, but they are not immunogenic. To circumvent this lack of immunogenicity and induce expansion of specific cytotoxic T lymphocytes (CTL), some investigators have proposed to use dendritic cells in cancer immunotherapy. Dendritic cells (DC) are unique professional antigen presenting cells that are able to uptake and cross-present class I and class II restricted antigens to CD8+ and CD4+ T lymphocytes. Importantly, mature DC are also capable of priming naive T lymphocytes through expression of costimulatories molecules (CD80, CD86). Proof of principle of the role of dendritic cells in clinical trials has been reported in normal volunteers by Dhodapkar (1). Indeed, DC pulsed with antigens, but not DC alone, nor peptides alone, were able to induce primary and to boost secondary antigen specific T cell based immune response. Some clinical trials using this strategy for metastatic cancer treatment have been reported. Using ex-vivo propagated DC, pulsed with either peptides or tumor cell lysates, Nestlé et al (2) reported 5 clinical responses in 16 melanoma Patients. Using fusion between DC and tumor cells, Kugler et al(3) reported 4 comliete responses in 17 metastatis renal cancer patients.