Therapeutics targeting tumor immune escape: Towards the development of new generation anticancer vaccines

Abstract

Despite the evidence that immune effectors can play a significant role in controlling tumor growth under natural conditions or in response to therapeutic manipulation, it is clear that malignant cells evade immune surveillance in most cases. Considering that anticancer vaccination has reached a plateau of results and currently no vaccination regimen is indicated as a standard anticancer therapy, the dissection of the molecular events underlying tumor immune escape is the necessary condition to make anticancer vaccines a therapeutic weapon effective enough to be implemented in the routine clinical setting. Recent years have witnessed significant advances in our understanding of the molecular mechanisms underlying tumor immune escape. These mechanistic insights are fostering the development of rationally designed therapeutics aimed at reverting the immunosuppressive circuits that undermine an effective antitumor immune response. In this review, the best characterized mechanisms that allow cancer cells to evade immune surveillance are overviewed and the most debated controversies constellating this complex field are highlighted. In addition, the latest therapeutic strategies devised to overcome tumor immune escape are described, with special regard to those entering clinical phase investigation.

Peptides in Melanoma Therapy

“…1): the cellular and molecular features of this biological scenario can ultimately tip the balance towards an effective immune response rather than immunological tolerance or even ignorance [99][100][101][102]. Based on this general concept, a variety of strategies have been devised to polarize the immune system against cancer: a comprehensive review of this ever growing field of research is beyond the scope of this article, and in this regard the readers are referred to dedicated review articles [103][104][105][106][107][108][109][110].…”

Training the Defense System for Modern-Day Warfare: The Horizons for Immunotherapy and Vaccines for Cancer

“…Cytotoxic T lymphocyte antigen 4-blocking monoclonal antibodies enhance immune activity by prolonging T-cell activation. Despite the evidence that immune effectors can play a significant role in controlling tumor growth under natural conditions or in response to therapeutic manipulation, it is unclear why malignant cells evade immune surveillance in most cases [5]. The field of immunotherapy is broadly composed of (a) Alternative Medicines-Chinese herbs, dietary supplements and homeopathic medicines, (b) Biological-Pharmaceutical grade products developed by biotechnology/drug companies that are clinically tested and require government approval/clearance for marketing.…”

Advances in Cellular Therapy for the Treatment of Thyroid Cancer

“…Another way of improving present treatment concepts is to use a combination therapy by which tumor cells are selectively affected and the tumor escape mechanisms are accessory blocked or decreased [146]. In this context, conventional chemotherapy has already been supported by a combination with DC vaccination showing some clinical benefits in nonendocrine tumors [147–149].…”