Newly Identified Tumor Antigens as Promising Cancer Vaccine Targets for Malignant Melanoma Treatment

P.F.      Ferrucci; G.      Tosti; A.      di Pietro; C.      Passoni; C.      Parii; I.      Tedeschi; F.      Cataldo; C.      Martinoli; A.      Testori

Abstract

Immunogenicity of tumour cells, immunomodulation and direct targeting of signalling pathways are promising avenues and matter of dated and innovative research in melanoma. Unfortunately, tumour cells are considered to be antigenic, but not immunogenic, either due to presentation of weakly recognized antigens or to the inability of the immune system to recognize them. However, spontaneous complete remission can be rarely observed in patients affected by melanoma, which are mainly attributed to the immune response against the tumour. Also, an elevated frequency of spontaneous humoral immune responses against tumour antigens was occasionally found in patients. These data confirm the existence of an interaction of the immune system with the tumour which can be used as a promising pathway for intervention and incorporates all portions of the immune system. The cancer immunotherapy approach is based on artificial activation of the immune system against the tumour and groups several types of treatments including immunization/vaccination but also modulation of immunity by cytokines or antibodies. Immunization approaches could either be based on undefined tumour antigens (e.g. whole tumour cells, tumour cell lysates, or tumour-antigen enriched fractions) or aimed at eliciting T-cell responses against specific tumour antigens. Novel and contemporary antigen-targeted therapy strategies, mainly directed to Cancer Testis and Heat Shock Proteins, leading to a possible active immunization against melanoma through Tcell specific activation, are discussed in this review.

Keywords: Melanoma, tumour antigens, immunization/vaccination, immunotherapy, cancer testis, MAGE A3, heat shock proteins, oncophage, spontaneous, tumour cell lysates, immunotherapeutic agents, immune-escape capacity, B-cell lymphoma, patient-tailored treatments, immunosuppressive cytokines