Exosomes in cancer immunotherapy: preclinical data
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.
Unable to display preview. Download preview PDF.
- 1.Dhodapkar MV, Steinman RM, Sapp M, Desai H, Fossella C, Krasovsky J, Donahoe SM, Dunbar PR, Cerundolo V, Nixon DF, Bhardwaj N, 2000, Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells.JClin Invest10: 19–14Google Scholar
- 3.Kugler A, Stuhler G, Walden P, Zoller G, Zobywalski A, Brossart P, Trefzer U, Ullrich S, Muller CA, Becker V, Gross AJ, Hemmerlein B, Kanz L, Muller GA, Ringert RH, 2000, Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids.Nat Med6: 332–6PubMedCrossRefGoogle Scholar
- 5.Regnault, A., Lankar, D., Lacabanne, V., Rodriguez, A., Thery, C., Rescigno, M., Saito, T., Verbeek, S., Bonnerot, C., Ricciardi-Castagnoli, P. and Amigorena, S., 1999, Fc gamma receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalizationJ. Exp. Med.189. 371–380PubMedCrossRefGoogle Scholar
- 11.Andersen MH, Graversen H, Fedosov SN, Petersen TE, Rasmussen JT, 2000, Functional analysis of two cellular binding domains of bovine lactadherin.Biochemistry39: 62006Google Scholar
- 12.Wolfers J, Andre F, Ruegg C, D. Shu, V. Serra, O. Dhellin, G. Raposo, C. Thery, S. Amigorena, J. Crouzet, T. Tursz and L. Zitvogel, 2000, Dendritic cell-derived exosomes are effective cancer vaccine: preclinical data towards a clinical trial.Proc Am Ass Cancer ResA5556Google Scholar
- 13.Wolfers J, Lozier A, Raposo G, Regnault A, Thery C, Masurier C, Flament C, Pouzieux S, Faure F, Tursz T, Angevin E, Amigorena S, Zitvogel L, 2001, Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming.Nat Medin pressGoogle Scholar