Tumor antigens for cancer immunotherapy: therapeutic potential of xenogeneic DNA vaccines

Srinivasan, Roopa; Wolchok, Jedd D.

doi:10.1186/1479-5876-2-12

Cited by 46 publications

(20 citation statements)

References 84 publications

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“…Self-antigens include differentiation (including Melan A in melanoma) and overexpressed antigens (including ErbB2 receptor tyrosine kinase 2 in colon, breast and lung cancer), whereas tumor-restricted antigens may be of viral origin (including human papilloma virus in cervical and throat cancer), from the germ line (including NY-ESO-1 in melanoma) or neoantigens (for example mutated antigens, including β-catenin in melanoma) ( 10 ). It is possible to induce immunization against tumor self-antigens, potentially generating an effective antitumor T-cell and antibody response ( 11 ).…”

Section: Cancer Immune Response: Host-protective While Tumor Promotinmentioning

confidence: 99%

HLA-mediated tumor escape mechanisms that may impair immunotherapy clinical outcomes via T-cell activation

Rodríguez

2017

Oncology Letters

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Although the immune system provides protection from cancer by means of immunosurveillance, which serves a major function in eliminating cancer cells, it may also lead to cancer immunoediting, molding tumor immunogenicity. Cancer cells exploit several molecular mechanisms to thwart immune-mediated death by disabling cellular components of the immune system associated with tumor recognition and rejection. Human leukocyte antigen (HLA) molecules are mandatory for the immune recognition and subsequent killing of neoplastic cells by the immune system, as tumor antigens must be presented in an HLA-restricted manner to be recognized by T-cell receptors. Impaired HLA-I expression prevents the activation of cytotoxic immune mechanisms, whereas impaired HLA-II expression affects the antigen-presenting capability of antigen presenting cells. Aberrant HLA-G expression by cancer cells favors immune escape by inhibiting the activities of virtually all immune cells. The development of cancer therapies based on T-cell activation must consider these HLA-associated immune evasion mechanisms, as alterations in their expression occur early and frequently in the majority of types of cancer, and have an adverse impact on the clinical response to immunotherapy. Herein, the concept of altered HLA expression as a mechanism exploited by tumors to escape immune control and induce an immunosuppressive environment is reviewed. A number of novel clinical immunotherapeutic approaches used for cancer treatment are also reviewed, and strategies for overcoming the limitations of these immunotherapeutic interventions are proposed.

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Section: Cancer Immune Response: Host-protective While Tumor Promotinmentioning

confidence: 99%

HLA-mediated tumor escape mechanisms that may impair immunotherapy clinical outcomes via T-cell activation

Rodríguez

2017

Oncology Letters

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“…Full length cDNA encoding the gene of interest is cloned into a bacterial plasmid vector under the control of a constitutively active promoter [160]. This plasmid is introduced into the host, either intra-dermally or intra-muscularly and is taken up by surrounding cells at the site of injection.…”

Section: B Dna Vaccinesmentioning

confidence: 99%

Targeting the Immune System in Cancer

Chaudhuri

Suriano²,

Mittelman³

et al. 2009

CPB

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The concept of cancer immunotherapy provides a fresh perspective as it is not associated with many of the drawbacks of conventional therapies such as chemotherapy, radiotherapy and surgery. When fully activated the immune system has immense potential as is evident from mis-matched transplanted organs undergoing rapid immunological attack and rejection. However, the development of immune strategies for cancer therapy has been associated with challenges of their own. Early attempts at cancer vaccination were carried out in an empirical manner that did not always lead to reproducibility. This led to a search of tumor associated antigens with the belief that specific targeting of these antigens would lead to successful tumor elimination. Active vaccination with TAA peptides or passive vaccination with specific lymphocytes against these TAAs did not however demonstrate encouraging results in clinical trials. This was mainly because of the lack of an activating immune response which is required for continuous stimulation of lymphocytes and also because of the selection of tumor escape variants that did not express the particular TAA. On the positive side, attempts at characterizing TAAs illuminated the molecular changes that attribute a malignant phenotype to cancer cells. Attempts at cytokine therapy were also met with challenges of high systemic toxicity and a lack of specific lymphocyte activation. It was therefore realized that an ideal vaccinating agent should be able to combine the effects of both these therapeutic strategies, i.e., it should be able to induce an innate immune response which can be tailored to a tumor specific adaptive immune response. By this, the immunosuppressive tumor environment can be altered to become immune activating, thus facilitating the infiltration of myeloid and lymphoid cells that can act in concert leading to tumor regression. In this regard, immunotherapeutic approaches such as DNA vaccines, dendritic cell based vaccines, HSP based vaccines and gene transfer technology, are being developed and further refined to overcome their inherent limitations. Animal experiments with these therapeutic modalities have demonstrated exciting results, although their evaluation in clinical trials has not indicated exceptional tumor protection in a large percentage of the patients. These observations only further underscore the multivariate and dynamic nature of the immune system and the many ways in which tumor cells modulate themselves and their surroundings to escape immune surveillance. Assessment of successful therapeutic intervention will require periodic evaluations of the suppressive nature of the tumor microenvironment accompanied by qualitative and quantitative measurements of lymphocyte responses in patients. With the development of advanced genetic technologies and continuous identification of tumor antigens, the field of cancer immunotherapy is progressing at an exciting pace giving us hope for the advent of effective treatment modalities that will prolong tumor free survival and enha...

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“…Immunization of mice with xenogeneic DNA coding for the human melanosomal membrane glycoprotein gp100 resulted in tumor protection and autoimmune depigmentation [124]. Immunization against defined tumor antigens using a homologous DNA source is currently being tested in early phase clinical trials for the treatment of melanoma and prostate cancers [125].…”

Section: Overcoming Tolerancementioning

confidence: 99%

Cancer Immunotherapy: Battling Tumors with Gene Vaccines

Chlichlia¹,

Schirrmacher²,

Sandaltzopoulos

2005

CMCAIAA

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Gene vaccines against defined antigens represent a novel and promising immunization approach for cancer immunotherapy and for battling infectious diseases. Immunization with plasmid DNA is the simplest gene-based approach. In order to induce protective antitumor immunity, gene vaccines are designed to deliver one or several genes encoding tumor-associated antigens, thereby eliciting or augmenting antigen-specific immune responses. The efficacy of gene vaccines can be significantly improved through integration of advances in immunology and molecular biology. Recent evidences point out the central role of dendritic cells and show the importance of innate immune responses in the induction and enhancement of antigen-specific adaptive immune responses. Hence, manipulations that integrate both tumorassociated antigens and 'danger' signals in the vaccine design, can achieve activation of both innate and adaptive immune responses, thereby overcoming the self-tolerance towards many tumor antigens. Coadministration of genetic adjuvants and optimized prime-boost strategies enhance the efficacy of gene vaccines. In this context, strategies that target antigens of choice to dendritic cells and induce, in vivo, antitumor immune responses are discussed. This review highlights vaccine strategies based on transfer of nucleic acid sequences encoding well-defined tumor-associated antigens and genetic adjuvants to the host in vivo in order to induce successful antitumor immunity.

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Tumor antigens for cancer immunotherapy: therapeutic potential of xenogeneic DNA vaccines

Cited by 46 publications

References 84 publications

HLA-mediated tumor escape mechanisms that may impair immunotherapy clinical outcomes via T-cell activation

HLA-mediated tumor escape mechanisms that may impair immunotherapy clinical outcomes via T-cell activation

Targeting the Immune System in Cancer

Cancer Immunotherapy: Battling Tumors with Gene Vaccines

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