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

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 T-cell specific activation, are discussed in this review.

Germ Cell Proteins in Melanoma: Prognosis, Diagnosis, Treatment, and Theories on Expression

“…However, until more is known about their function, the related therapies primarily revolve around germ cell protein immunogenicity. Tumor cells are generally considered antigenic but not immunogenic, allowing them to evade host immune defenses [30]. Recent cancer immunotherapy approaches focus on activating an immune response to cancer cell antigens.…”

Natural Killer (NK)- and T-Cell Engaging Antibody-Derived Therapeutics

“…Considering the dismal alternatives for patients with metastatic melanoma, the clinical benefit achieved by this agent was sufficient to merit drug approval and the agent is now in routine clinical use. It is one of the very few successful treatments for metastatic melanoma, even if the success may be considered modest [64,68].…”

A four-marker signature of TNF-RII, TGF-α, TIMP-1 and CRP is prognostic of worse survival in high-risk surgically resected melanoma

“…The role of vaccination with proteins and peptides has been an area of intense interest [6-8], however many of these studies have been hampered by modest clinical benefits despite initially promising results [7,9,10]. One of the mechanisms involved in immune escape by melanoma cells involves down regulation of the proinflammatory microenvironment by regulatory T cells (T reg ) via the release of immunosuppressive cytokines such as IL-10 and TGF-β, among several other immune suppressive mechanisms [9,11]. Type II cytokines such as IL-6, TNF-α, IFN-γ and IL-10 have also been shown to be important regulators of melanoma immune tolerance and escape [12].…”