Melanoma vaccines: The problems of local immunosuppression
Section snippets
How melanoma avoids immune recognition: Current theories
The complex interactions between the immune system and developing malignancies have been studied by many. The fact that immunogenic tumors such as melanoma develop in otherwise immunocompetent patients and the coexistence of tumor-specific immunity with a progressing tumor remain among the major paradoxes of tumor immunology [21], [22]. Among several theories that have been constructed to explain this paradox, those most commonly quoted are those of immune surveillance [23], recently updated to
Strategies for evoking anti-melanoma immune response
Activation of the immune response requires recognition of an immunogenic molecule, and if the memory response is to be generated, it is necessary that the antigen is presented in the context of HLA class II molecules by an APC to T lymphocytes, supported by co-stimulatory signals. To find suitable antigens for vaccine purposes, melanoma proteins have been screened for peptides with potent immunostimulatory characteristics, presented by both HLA class I and II, to activate both cytotoxic and
Melanoma vaccines—a lesson from uveal melanoma
Uveal melanoma is another aggressive malignancy originating from melanocytes. Because this tumor arises in an immunoprivileged site, it is interesting to analyze how this affects uveal melanoma immunogenicity and whether immunotherapy will be feasible.
Thanks to its privileged localization, uveal melanomas can safely express tumor-associated antigens [96], [97], and HLA class I molecules [98], to which the host is not tolerized [99]; hence it constitutes a potent stimulus for anti-melanoma
Melanoma vaccines–future possibilities
Although some mechanisms for interaction between a melanoma and the immune system have been discovered, including alteration of DC function and maturation by tumor-derived cytokines leading to the generation of suppressive and regulatory T lymphocytes, the exact molecular pathways need to be investigated. Investigations of the local and systemic immune suppression within melanoma will allow the dissection of discriminating immune system–related key events in melanoma progression, and generate
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2017, Cancer LettersCitation Excerpt :The main cause of death is from widespread metastases to the lymphatic system and other vital organs [4]. The 5-year survival rate is close to 90% for localized melanoma but less than 20% for metastatic melanoma with a median survival rate of 6–9 months [5]. Therefore, significant research efforts have been devoted to discovering new therapies for this aggressive skin malignancy.
Robust expansion of dendritic cells in vivo by hydrodynamic FLT3L-FC gene transfer
2014, Journal of Immunological MethodsCitation Excerpt :Due to its short plasma half-life (1.4 h following 10 μg i.p. injection, Fig. 1A); note a slightly longer t1/2 of 5.2 h following 5 μg FLT3L injected i.m. was reported (Robinson et al., 2003), repeated daily injections with recombinant FLT3L protein (Karsunky et al., 2003) or implantation of FLT3L-secreting tumor cells (Mach et al., 2000) is necessary to achieve sufficient levels of FLT3L for effective DC expansion in vivo. Limitations to these approaches include expense and labor for the former, or generating DC in the context of rapidly growing tumors that can secrete factors and alter DC function (Polak et al., 2009), for the latter. We therefore sought to engineer FLT3L to extend its in vivo half-life, and then combine this improved reagent with a simple and cost-effective recombinant DNA-based overexpression method (hydrodynamic gene transfer) to effectively boost DC numbers in vivo.
Review and cross-validation of gene expression signatures and melanoma prognosis
2012, Journal of Investigative DermatologyLong-term survivors after immunotherapy for metastatic melanoma
2011, Immunology LettersEnhancing therapy of B16F10 melanoma efficacy through tumor vaccine expressing GPI-anchored IL-21 and secreting GM-CSF in mouse model
2010, VaccineCitation Excerpt :The strong contribution of the tumor vaccine B16F10/IL-21-gpi-GM-CSFs to the therapeutic efficacy might also be its action on the tumor microenvironment. It has become increasingly clear that melanoma cells have the ability to inhibit the immune system by inducing an immunosuppressive microenvironment that may explain the inability of systemic vaccines to alter patient outcomes [28]. In our current investigation, the developed tumor cell vaccine, which not only expressed GPI-anchored IL-21 but also secreted GM-CSF, can release IL-21 from the GPI-anchored to tumor microenvironment so that high concentration of IL-21 was achieved in the tumor tissue locally, and its half-life might be extended due to the role of GPI-anchored, and local IL-21 immune therapeutic effect was more prolonged in vivo.