Editorial [Hot topic: New Generation Cancer Vaccines: From Tumor Immunology to Clinical Applications (Executive Editor: Simone Mocellin)]

Active specific immunotherapy holds great potential in the search for new therapeutic approaches for patients with cancer. Much preclinical and clinical evidence has shown that the immune system can be polarized against malignant cells by several vaccination strategies. Exploiting a naturally occurring defense system, anticancer vaccination embodies an ideal non-toxic treatment for cancer that has been nourishing the hope of curing this disease for more than half a century. Despite the evidence that immune effectors can play a significant role in controlling tumor growth either in natural conditions or in response to therapeutic manipulation, the cascade of molecular events leading to tumor rejection by the immune system remains to be fully elucidated. Nevertheless, some recent tumor immunology advancements might drastically change the way to design the next generation of cancer vaccines, hopefully improving the effectiveness of this therapeutic approach. Although at present no anticancer vaccine can be recommended outside clinical trials, tumor response and immunological findings in animals and humans should prompt researchers to investigate further the potential of this biotherapy. In this issue of Current Pharmaceutical Design, the Authors address some of the most debated and crucial aspects regarding the preclinical development and clinical implementation of anticancer vaccines based on the latest tumor immunology molecular insights. In particular the articles describe the rationale of some of the most promising strategies to circumvent tumor immune escape mechanisms and thus to improve the clinical efficacy of active specific immunotherapy against malignancies. Zwirner N. and Rabinovich G. [1] from the Immunology Laboratory of the Buenos Aires University (Buenos Aires, Argentina) introduce the topic of the intricate network of interactions between tumor and immune cells that have revealed novel regulatory signals, including cell surface inhibitory receptors and costimulatory molecules, intracellular regulatory pathways, immunosuppressive cytokines and proapoptotic mediators, which may operate in concert to orchestrate tumor-immune escape. The Authors critically discuss how the control of the effector functions of innate and adaptive immune cells and the manipulation of regulatory pathways, either alone or in combination, could be exploited for therapeutic purposes in cancer patients. Dubovsky J. and Sotomayor E. [2] from the Department of Immunology and Department of Malignant Hematology of the Lee Moffitt Cancer Center (Tampa, FL, USA) focus first on the current understanding of the tenants of a good tumor antigen and how epigenetic manipulation of tumor cells might provide the long elusive “ideal antigen” with none or minimal tolerogenic potential. Then, the Authors comment on the emerging role of hystone deacetylase inhibitors and their targets in regulating inflammatory responses in antigen presenting cells as well as malignant cells themselves. The metabolic immune restraints that may hinder an appropriate immune response to anticancer vaccines - an emerging aspect of tumor immune escape - are discussed by Mocellin S. [3] from the Department of Oncological and Surgical Sciences of the University of Padova (Padova, Italy). The development of agents interfering with this phenomenon and thus potentially useful to increase the therapeutic effect of cancer vaccines is overviewed, providing readers with a comprehensive list of references regarding both preclinical and clinical evidences. Guinipero T. and Finn O. [4] from the Departments of Immunology and Pediatrics of the University of Pittsburgh (Pittsburgh, PA, USA) outline an interesting and somewhat unexpectedly neglected research field such as that of cancer vaccination in the pediatric population. Due to the greater capacity of a young immune system to recover after cancer treatment, therapeutic vaccines are expected to have a better chance to elicit protective immunity and prevent cancer recurrence in children. In this review, the Authors describe the current efforts at designing and testing cancer vaccines in children with the focus on specific tumor antigens expressed by pediatric cancers. Finally, Inoges S. and Bendandi M. [5] from Laboratory of Immunotherapy of the University of Navarra (Pamplona, Spain) and the Simmons Comprehensive Cancer Center of the University of Texas (Dallas, TX, USA) address another key issue such as the development of therapeutic vaccines against hematological cancers. In particular, the Authors focus on the preclinical evidence and clinical implementation of idiotype vaccines for B-cell malignancies, which are characterized by the unique feature of carrying tumor-specific antigenic sites such as the idiotopes found within the hypervariable regions of the immunoglobulin variable domain. Overall, this Current Pharmacology Design issue provides readers with an authoritative overview on some of the most interesting and critical aspects that must be faced by both basic researchers and clinical oncologists involved cancer vaccine development.