An open-label, prospective phase I/II study evaluating the immunogenicity and safety of a ras peptide vaccine plus GM-CSF in patients with non-small cell lung cancer

Meyer, Ralf G.; Korn, Stephanie; Micke, Patrick; Becker, Kai; Huber, Christoph; Wölfel, Thomas; Buhl, Roland

doi:10.1016/j.lungcan.2007.05.003

Cited by 24 publications

(20 citation statements)

References 46 publications

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“…A recurring observation in many late-stage cancer vaccine trials has been that some patients experience a peripheral tumor-specific immune response without apparent clinical benefit (Powell et al ., 2006; Johnson et al ., 2007; Meyer et al ., 2007; Slingluff et al ., 2007). This may be due to a specific immunoresistant phenotype that precludes T-cell-mediated killing of tumor target.…”

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confidence: 99%

“…These patients may therefore be resistant to currently used T-cell-mediated immunotherapies, including peptide (Meyer et al ., 2007; Slingluff et al ., 2007)- or antibody (Small et al ., 2007)-based vaccines. Currently, the selection of patients for immunotherapy protocols does not take into account the immunoresistant phenotype of a tumor, with emphasis placed instead on criteria such as antigen expression and histology.…”

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confidence: 99%

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PI(3) kinase is associated with a mechanism of immunoresistance in breast and prostate cancer

et al. 2008

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Immune escape describes a critical event whereby tumor cells adopt an immunoresistant phenotype to escape adaptive surveillance. We show that expression of a pivotal negative regulator of T-cell function, B7-H1, correlates with PI(3) kinase activation in breast and prostate cancer patients. B7-H1-mediated immunoresistance can be attenuated by inhibitors of the PI(3) kinase pathway, and is dependent on S6K1-mediated translational regulation of B7-H1 protein. Breast and prostate carcinoma cells with activated PI(3) kinase lose the immunoresistant phenotype after treatment with B7-H1 siRNA. Conversely, breast and prostate carcinoma cells with minimal PI(3) kinase activation adopt an immunoresistant phenotype when engineered to overexpress B7-H1 protein. These observations describe a mechanism for immune escape from tumor dormancy in humans that relates to oncogenesis.

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confidence: 99%

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PI(3) kinase is associated with a mechanism of immunoresistance in breast and prostate cancer

et al. 2008

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“…Mutations in the K-RAS gene, mainly in codons 12 and 13, have been found in 20-30% of NSCLC tumor samples and occur most commonly, but not exclusively, in adenocarcinoma histology and in heavy smokers. Active immune strategies aimed at interfering with the Ras-Raf-MEK pathway in NSCLC are also incipient exploring the use of a Ras peptide based vaccine [40]. …”

Section: Nsclc Biology and Target Antigens For Cancer Vaccinesmentioning

confidence: 99%

Challenges and Opportunities for Cancer Vaccines in the Current NSCLC Clinical Scenario

Rodríguez

Sánchez²

2013

CTMC

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This review is aimed to focus on NSCLC as an emerging and promising model for active immunotherapy and the challenges for its inclusion in the current clinical scenario. Cancer vaccines for NSCLC have been focused as a therapeutic option based on the identification of a tumor hallmark and the active immunization with the related molecules that triggers cellular and/or humoral responses that consequently destroy or delay the rate of malignant progression. This therapeutic intervention in an established disease state has been aimed to impact into prolonging patient´s survival with ethically accepted quality of life. Understanding of relationship between structure and function in cancer vaccines is essential to interpret their opportunities to impact into prolonging survival and increasing quality of life in cancer patients. It is widely accepted that the failure of the cancer vaccines in the NSCLC scenario is related with its introduction in the advanced disease stages and poor performance status of the patients due to the combination of the tumor induced immunosuppression with the immune senescence. Despite first, second and emerging third line of onco-specific treatments the life expectancy for NSCLC patients diagnosed at advanced stages is surrounding the 12 months of median survival and in facts the today real circumstances are extremely demanding for the success inclusion of cancer vaccines as therapeutic choice in the clinical scenario. The kinetics of the active immunizations encompasses a sequential cascade of clinical endpoints: starting by the activation of the immune system, followed by the antitumor response and finalizing with the consequential impact on patients’ overall survival. Today this cascade of clinical endpoints is the backbone for active immunization assessment and moreover the concept of cancer vaccines, applied in the NSCLC setting, is just evolving as a complex therapeutic strategy, in which the opportunities for cancer vaccines start from the selection of the target cancer hallmark, followed by the vaccine formulation and its platforms for immune potentiating, also cover the successful insertion in the standard of care, the chronic administration beyond progression disease, the personalization based on predictors of response and the potential combination with other targeted therapies.

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“…Therefore, mutant RAS proteins are an attractive target for vaccine therapy, and there are ongoing clinical trials using this approach 103 104…”

Section: Ras Mutations As a Therapeutic Targetmentioning

confidence: 99%

How molecular pathology is changing and will change the therapeutics of patients with follicular cell-derived thyroid cancer: Table 1

et al. 2009

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Well-differentiated thyroid carcinomas comprise two well-defined histological types: papillary and follicular (PTCs and FTCs, respectively). Despite being derived from the same cell (thyroid follicular cell), these two types of tumour accumulate distinct genetic abnormalities during progression. The molecular pathology of thyroid cancer is now better understood because of our ability to identify RET/PTC rearrangements and BRAF mutations in the aetiopathogenesis of the large majority of PTCs and the high prevalence of RAS mutations and PAX8/PPARgamma rearrangements in follicular patterned carcinomas (FTCs and follicular variant of PTCs). This review summarises most of the molecular alterations currently used as targets for new biological treatments and looks at some of the changes that are already occurring or may occur in the treatment of patients with thyroid cancer. For simplicity, the review is divided up according to the major genetic alterations identified in well-differentiated thyroid carcinomas (RET/PTC rearrangements, BRAF mutations, RAS mutations and mitochondrial DNA deletions and mutations) and their respective treatments.

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An open-label, prospective phase I/II study evaluating the immunogenicity and safety of a ras peptide vaccine plus GM-CSF in patients with non-small cell lung cancer

Cited by 24 publications

References 46 publications

PI(3) kinase is associated with a mechanism of immunoresistance in breast and prostate cancer

PI(3) kinase is associated with a mechanism of immunoresistance in breast and prostate cancer

Challenges and Opportunities for Cancer Vaccines in the Current NSCLC Clinical Scenario

How molecular pathology is changing and will change the therapeutics of patients with follicular cell-derived thyroid cancer: Table 1

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