Nuevos avances en vacunas contra el cáncer!!!!! expert-reviews/doi/full/10.1586/17476348.2013.838013 Although significant progress has been made in the treatment of cancer over the last two decades, very often clinical benefit is still marginal and of limited duration. Cancer treatment has seen the emergence of selective, mechanism-based therapeutics (so-called targeted therapies), capable of inhibiting molecular pathways deregulated in cancer cells and responsible for tumor growth and maintenance. These targeted therapies are indeed able to induce immediate and often striking objective responses which, unfortunately, rapidly wane due to selection of resistant clones bearing additional mutations or epigenetic changes which activate escape pathways [1]. Therefore, there is the need to develop alternative approaches to control cancer. In this context, immunotherapies based on the use of inhibitors of immunological check points or on anticancer vaccines may represent an important alternative. This special focus issue on ‘New developments in Cancer Vaccines’ will focus only on the second topic. To date, three cancer vaccines have been licensed. Two of them are very successful cancer preventive agents, targeting tumor-associated viral agents (anti-HBV, to prevent HBV-associated hepatocellular carcinoma [2] and anti-HPV, to prevent HPV-associated cervical carcinoma [3,4], respectively). The third is Dendreon’s Provenge®, which is the only therapeutic cancer vaccine approved by the USA. regulatory Agency FDA for the treatment of metastatic hormone-refractory prostate cancer [5,6]. Although this vaccine represents an important proof of concept, it is able to induce a limited improvement in overall survival, with associated elevated costs of production, which indicates that significant improvements are needed. To this aim, several concurrent strategies could be adopted including: identification of novel and more specific tumor-associated antigens (including personalized ones); inhibition of tumor suppressive microenvironment; selection of appropriate adjuvant; selection of efficient delivery and presentation systems; and understanding of molecular mechanisms ruling the response to vaccines. This special focus issue on ‘New developments in Cancer Vaccines’ includes a series of timely in-depth reviews written by leaders in the field, which cover most of the recent strategies addressing key aspects in improving the efficacy of cancer vaccines. It is mostly dedicated to concepts in the developmental stage of candidate vaccines not yet fully established and validated in human clinical trials. • Bracci et al., address the potential role of the different subtypes of dendritic cells (DCs) for designing effective immunotherapeutic cancer vaccines [7]. Indeed, although a large number of clinical studies have been carried out, a consensus on the optimal treatment with DCs has not been reached yet. • Bot et al., have focused on the appropriate positioning of cancer vaccination, within the cancer therapeutic strategies, according to individual clinical condition [8]. This aspect is of strategic relevance in order to dramatically improve the final clinical outcome in cancer patients. • Rammensee and Singh-Jasuja describe the most recent updates on the exploitation of the human leukocyte antigen (HLA) ligandome for identifying tumor antigens to develop personalized cancer vaccines [9]. This approach holds great promises with regards to selection of the optimal and effective target antigens to be used in the vaccine development. • Elsedawy and Russell provide a state-of-the-art review on oncolytic viruses as cancer vaccines [10]. Such platform is a promising strategy resulting in both direct killing of tumor cells and providing a large array of released tumor antigens as well as danger signals, to promote an effective immune response. • The potential use of live attenuated bacterial vectors as delivery system for tumor antigens is addressed by Chaucet et al. [11]. This has been explored in several clinical trials, in particular using Listeria or Salmonella spp, supporting further development. • Aurisicchio et al., describe the recent promising results in induction of cellular immunity specific to tumor antigens by in vivo injection of nucleic acids [12]. These results are closely related to new developments in DNA vectors as well as electro gene-transfer strategies. • The efficacy of virus-like particles (VLPs) and particles in presenting and delivering tumor antigens to antigen-presenting cells is described by Ungaro et al. [13]. Such strategy is effective for preventive as well as therapeutic vaccine approaches, offering an extremely broad and versatile technological platform. The first two preventive cancer vaccines (HBV and HPV vaccines) are, indeed, based on VLPs. • Finally, the two editorials by Berzofsky et al. and Parmiani et al. are focused on strategies to improve the immune responses elicited by cancer vaccines, which is a field of active investigation by several groups [14,15]. In conclusion, effective therapeutic cancer vaccines are still an ongoing quest. However, the success of anticancer vaccines very likely will rely on close collaboration between experts from the different fields who will concur to shed lights on aspects not yet fully understood but essential to reach the final goal. Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript. References 1 Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nat. Rev. Cancer 12(4), 237–251 (2012). [CrossRef] [Medline] [CAS] 2 Chang MH, Chen CJ, Lai MS et al. Universal hepatitis B vaccination in Taiwan and the incidence of hepatocellular carcinoma in children. Taiwan Childhood Hepatoma Study Group. N. Engl J. Med. 336(26), 1855–1859 (1997). [CrossRef] [Medline] [CAS] 3 Harper DM, Franco EL, Wheeler CM et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 367(9518), 1247–1255 (2006). [CrossRef] [Medline] [CAS] 4 The FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N. Engl J .Med. 356(19), 1915–1927 (2007). [CrossRef] [Medline] 5 Kantoff PW, Higano CS, Shore ND et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl J. Med. 363(5), 411–422 (2010). [CrossRef] [Medline] [CAS] 6 Small EJ, Sacks N, Nemunaitis J et al. Granulocyte macrophage colony-stimulating factor – secreting allogeneic cellular immunotherapy for hormone-refractory prostate cancer. Clin. Cancer Res. 13(13), 3883–3891 (2007). [CrossRef] [Medline] [CAS] 7 Bracci L, Capone I, Moschella F, Proietti E, Belardelli F. Exploiting dendritic cells in the development of cancer vaccines. Expert Rev. Vaccines 12(10), 1109–1110 (2013). 8 Bot A, Marincola F, Smith KA. Repositioning therapeutic cancer vaccines in the dawning era of potent immune interventions. Expert Rev. Vaccines 12(10), 1219–1234 (2013). [Abstract] 9 Rammensee HG, Singh-Jasuja H. HLA-ligandome tumor antigen discovery for personalized vaccine approach. Expert Rev. Vaccines 12(10) 1211–1217 (2013). [Abstract] 10 Elsedawy NB, Russell SJ. Oncolytic vaccines. Expert Rev. Vaccines 12(10), 1155–1172 (2013). [Abstract] 11 Chauchet X, Wang Y, Polack B, Toussaint B, Le Gouellec A. Live attenuated bacteria as a cancer vaccine vector Expert Rev. Vaccines 12(10), 1139–1154 (2013). 12 Aurisicchio L, Mancini R, Ciliberto G. Cancer vaccination by electro-gene-transfer. Expert Rev. Vaccines 12(10), 1127–1137 (2013). [Abstract] 13 Ungaro F, Conte C, Quaglia F, Tornesello ML, Buonaguro FM, Buonaguro L. VLPs and particle strategies for cancer vaccines. Expert Rev. Vaccines 12(10), 1173–1193 (2013). [Abstract] 14 Berzofsky JA, Wood LV, Terabe M. Cancer Vaccines: 21st century approaches to harnessing an ancient modality to fight cancer. Expert Rev. Vaccines 12(10), 1115–1118 (2013). [Abstract] 15 Parmiani G, Cimminiello C, Maccalli C. Increasing immunogenicity of cancer vaccines to improve their clinical outcome. Expert Rev. Vaccines 12(10), 1111–1113 (2013). [Abstract]
Posted on: Wed, 13 Nov 2013 03:11:44 +0000
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