The cancer vaccine roller coaster

Goldman, Bruce; DeFrancesco, Laura

doi:10.1038/nbt0209-129

Cited by 158 publications

(121 citation statements)

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“…1 To escape surveillance by the immune system, tumor cells are able to co-opt multiple immunosuppressive pathways 2 , 3 such as the engagement of immune checkpoints that prevents an effective anti-tumor immunity. Immunotherapy aims to stimulate anti-tumor activity by reactivating the immune system.…”

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confidence: 99%

High-dimensional mass cytometry analysis revealed microenvironment complexity in chronic lymphocytic leukemia

et al. 2018

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High-dimensional mass cytometry analysis revealed microenvironment complexity in chronic lymphocytic leukemia

et al. 2018

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“…A limited number of products have been approved for use in various countries (reviewed in [20]), although not usually in multiple countries. These have been based on a variety of approaches, but have mainly involved administration of cellular products rather than traditional off-the-shelf biologicals.…”

Section: Licensed Cancer Vaccinesmentioning

confidence: 99%

Cancer vaccines

Liu¹

2011

Phil. Trans. R. Soc. B

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While vaccines are primarily thought of in terms of their use for prevention of infectious diseases, they can potentially be used to prevent or treat cancer. This manuscript explores the rationale for vaccines and immunotherapies for cancer from both the scientific and the global needs perspectives. Pathogens that are aetiologic agents of certain cancers provide perhaps the most obvious successful examples of the prophylactic utility of vaccines (such as the hepatitis B vaccine) to prevent not just the infectious disease (hepatitis), but the potential subsequent cancer (hepatocellular carcinoma). The use of monoclonal antibodies illustrates the effectiveness of the immune system for cancer therapy. In addition, the increased understanding of the role and mechanisms of the immune system in the processes of immune surveillance, as well as of its failure during immunosuppression, have yielded better insights into how to design cancer vaccines and immunotherapies. Examples of targets for cancer vaccines will be discussed, as will the challenges and few successes in this arena.

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“…Thus, class I MAGEs became ideal targets for immunotherapies considering their specific expression in a large variety of cancer cells and their contribution to the development of malignancies (Chomez et al, 2001;Simpson et al, 2005). Emerging data have focused on the potential of MAGE proteins as targets of anti-tumor antibodies and as preemptive anticancer vaccines (Brichard and Lejeune, 2007;Goldman and DeFrancesco, 2009). While the limited expression pattern and potential for immunotherapy of MAGE proteins have been investigated extensively, the more fundamental question concerning the physiologic function and mechanism of MAGE proteins has long been overshadowed.…”

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confidence: 99%

“…It will be interesting to examine whether the binding MAGE proteins also stimulate the ubiquitin ligase activity of these RING domain E3s, as well as many other uncharacterized RING domain E3 proteins that bind MAGEs. MAGE cancer testis antigens have been targeted by antibody and vaccine therapies due to their specific antigen presentation on cancer cells (Brichard and Lejeune, 2007;Goldman and DeFrancesco, 2009). However, due to the lack of knowledge of how MAGE cancer testis antigens function in cells, the development of inhibitors of MAGE cancer testis antigens within cells has been unexplored.…”

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confidence: 99%

When MAGE meets RING: insights into biological functions of MAGE proteins

2011

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The melanoma antigen (MAGE) family proteins are well known as tumor-specific antigens and comprise more than 60 genes, which share a conserved MAGE homology domain (MHD). Type I MAGEs are highly expressed cancer antigens, and they play an important role in tumorigenesis and cancer cell survival. Recently, several MAGE proteins were identified to interact with RING domain proteins, including a sub-family of E3 ubiquitin ligases. The binding mode between MAGEs and RING proteins was investigated and one important structure of these MAGE-RING complexes was solved: the MAGE-G1-NSE1 complex. Structural and biochemical studies indicated that MAGE proteins could adjust the E3 ubiquitin ligase activity of its cognate RING partner both in vitro and in vivo. However, the underlying mechanism was not fully understood. Here, we review these exciting advances in the studies on MAGE family, suggest potential mechanisms by which MAGEs activate the E3 activity of their binding RING proteins and highlight the anticancer potential of this family proteins. KEYWORDS MAGE, cancer testis antigen, RING, ubiquitin ligase, TRIM28 OVERVIEW OF THE MAGE FAMILY PROTEINSThe cancer/testis antigens are types of proteins that appear to be only present in germline cells, trophoblasts and tumors (Simpson et al., 2005). It is also implicated that aberrant expression of germline genes in cancer cells might be one of the driving forces of tumorigenesis. The family of cancer/testis antigens has undergone expansion during the past years, and now consists of more than 100 genes, with new members still being identified (Scanlan et al., 2004;Doyle et al., 2010). Cancer/testis antigen genes are widely expressed in various types of tumors, such as melanoma, carcinoma of the bladder and liver (Barker and Salehi, 2002;Miranda, 2010). These immunogenic features have endowed them the potential as therapeutic cancer vaccines (Simpson et al., 2005). Typically, this family is divided into three sub-families: melanoma antigen (MAGE), G antigen (GAGE), and X chromosome antigen (XAGE) families. The majority of these genes exist as multigene families, and are often under similar transcriptional regulation, leading to their co-expression in some contexts (Scanlan et al., 2002).The first identified member of this family, MZ2-E, was discovered in a patient with melanoma who had cytotoxic T cell recognizing tumor cells (van der Bruggen et al., 1991;Simpson et al., 2005). This gene was later found to belong to a 12-hMAGE-A genes cluster, and thus known as MAGE-A1 (Chomez et al., 2001). Since then, the MAGE family has extensively increased and more than 60 genes have been identified in humans up to now. Based on their different expression patterns, the MAGE family genes are subdivided into two categories. The type I MAGE genes are located in clusters of the X chromosome, and consist of MAGE-A, -B, and -C groups, with their expression restricted to testis, trophoblast, and placenta (Barker and Salehi, 2002;Simpson et al., 2005). Unlike MAGE I genes, type II MAGE gene...

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The cancer vaccine roller coaster

Cited by 158 publications

References 5 publications

High-dimensional mass cytometry analysis revealed microenvironment complexity in chronic lymphocytic leukemia

High-dimensional mass cytometry analysis revealed microenvironment complexity in chronic lymphocytic leukemia

Cancer vaccines

When MAGE meets RING: insights into biological functions of MAGE proteins

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