Expression of defined genes identified by pretreatment tumor profiling: Association with clinical responses to the GSK MAGE- A3 immunotherapeutic in metastatic melanoma patients (EORTC 16032–18031)

Louahed, Jamila; Gruselle, Olivier; Gaulis, Swann; Coche, Thierry; Eggermont, A.M.M.; Kruit, W.; Dréno, Brigitte; Sileni, V. Chiarion; Lehmann, F; Brichard, Vincent G.

doi:10.1200/jco.2008.26.15_suppl.9045

Cited by 47 publications

(32 citation statements)

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“…Quantitative reverse transcription PCR was later used to confirm the high expression of immune-related genes in patients with improved clinical outcome. 16 These findings suggest that a subset of patients have pro-inflammatory infiltrates of T cells and chemokines in their tumors, making them more susceptible to immunotherapeutic interventions, a tumor vaccine in this case. Further, a phase II study in surgically resected stage IB or II non-small cell lung cancer evaluated the MAGE-A3 recombinant protein in 182 patients with MAGE-A3-positive tumors.…”

Section: Discussionmentioning

confidence: 90%

“…Microarray gene expression profiling was performed on baseline biopsies. 16 A proinflammatory signature was found to be associated with a significant improvement in median OS; 16.2 mo in signature (-ve) versus 28 mo in signature (Cve) patient population. Quantitative reverse transcription PCR was later used to confirm the high expression of immune-related genes in patients with improved clinical outcome.…”

Section: Discussionmentioning

confidence: 92%

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Expression profiles of immune-related genes are associated with neoadjuvant ipilimumab clinical benefit

Tarhini

Lin

et al. 2017

OncoImmunology

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 92%

Expression profiles of immune-related genes are associated with neoadjuvant ipilimumab clinical benefit

Tarhini

Lin

et al. 2017

OncoImmunology

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“…A number of large scale clinical trials tried to validate these tools, such as specific gene profiles, which appear to be potentially associated with different prognoses [141][142][143]. In particular, starting from tumour biopsies of patients enrolled in the Phase II melanoma trial, an attempt was made to identify a gene signature that may predict a favourable clinical outcome for those treated with the recMAGE-A3 + AS15 ASCI [144].…”

Section: Identification Of a Specific Melanoma Gene Signaturementioning

confidence: 99%

Newly Identified Tumor Antigens as Promising Cancer Vaccine Targets for Malignant Melanoma Treatment

Ferrucci¹,

Tosti²,

Pietro³

et al. 2012

CTMC

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Immunogenicity of tumour cells, immunomodulation and direct targeting of signalling pathways are promising avenues and matter of dated and innovative research in melanoma. Unfortunately, tumour cells are considered to be antigenic, but not immunogenic, either due to presentation of weakly recognized antigens or to the inability of the immune system to recognize them. However, spontaneous complete remission can be rarely observed in patients affected by melanoma, which are mainly attributed to the immune response against the tumour. Also, an elevated frequency of spontaneous humoral immune responses against tumour antigens was occasionally found in patients. These data confirm the existence of an interaction of the immune system with the tumour which can be used as a promising pathway for intervention and incorporates all portions of the immune system. The cancer immunotherapy approach is based on artificial activation of the immune system against the tumour and groups several types of treatments including immunization/vaccination but also modulation of immunity by cytokines or antibodies. Immunization approaches could either be based on undefined tumour antigens (e.g. whole tumour cells, tumour cell lysates, or tumour-antigen enriched fractions) or aimed at eliciting T-cell responses against specific tumour antigens. Novel and contemporary antigen-targeted therapy strategies, mainly directed to Cancer Testis and Heat Shock Proteins, leading to a possible active immunization against melanoma through T-cell specific activation, are discussed in this review.

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“…36 A gene signature derived from pretreatment tumor biopsies predicted clinical benefit in a study of a recombinant MAGE-A3 fusion protein (EORTC 16032-18031) in the treatment of melanoma. 37 A DC vaccine study in colon cancer patients identified a prevaccination plasma protein signature (sgp130, CXCL11, CD62L, membrane cofactor protein-1, and IL-20) that predicted responses to DC vaccination. 38 Much work has to be done before correlative studies validating prediction markers can be realized.…”

Section: Future Perspectivesmentioning

confidence: 99%

Cellular Vaccine Approaches

2010

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Therapeutic cancer vaccines aim to generate immunologic targeting of cancer cells through the induction of effective cellular and antibody-mediated responses specific for antigens selectively expressed by the tumor. Exploiting the adaptive immune system as a targeted tool against cancer is appealing in its capacity for exact specificity and avoidance of unintended tissue damage seen by other conventional agents such as chemotherapy. There are a multitude of challenges to designing effective vaccine strategies. The components of a vaccine strategy start with the challenges of selecting immunogenic, tumor-specific antigen targets, choosing a platform with which to deliver the antigens, and enhancing the immunostimulatory context in which the vaccines are delivered. Although understanding the components of effective T-cell activation is essential, successful effector T cells can only be produced if there is also an understanding of the natural processes that tumors exploit to down-modulate active immune responses. These processes are normally used to down-regulate excessive tissue-destructive immune responses against infectious agents once the infecting agent is cleared or to prevent autoimmunity. Advances in molecular and cellular technologies continue to provide insights into the regulation of immune responses both to infectious agents and to cancer that may be manipulated to tip the balance in favor of tumor regression over immune tolerance. This review focuses primarily on cellular vaccines. For the purpose of this review, cellular vaccines are defined as vaccines that use whole cells or cell lysates either as the source of antigens or the platform in which to deliver the antigens. Dendritic cell (DC)-based vaccines focus on ex vivo antigen delivery to DCs. Other platforms such as GVAX (tumor cells genetically engineered to produce granulocyte-macrophage colony-stimulating factor) aim to deliver tumor antigens in vivo in an immune stimulatory context to endogenous DCs. Because data continue to emerge regarding the importance of the maturation status of DCs and the importance of the particular subset of DCs being targeted, these insights will be integrated into vaccine strategies that are likely to produce more effective vaccines.

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Expression of defined genes identified by pretreatment tumor profiling: Association with clinical responses to the GSK MAGE- A3 immunotherapeutic in metastatic melanoma patients (EORTC 16032–18031)

Cited by 47 publications

References 0 publications

Expression profiles of immune-related genes are associated with neoadjuvant ipilimumab clinical benefit

Expression profiles of immune-related genes are associated with neoadjuvant ipilimumab clinical benefit

Newly Identified Tumor Antigens as Promising Cancer Vaccine Targets for Malignant Melanoma Treatment

Cellular Vaccine Approaches

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