Efficacy of systemic adoptive transfer immunotherapy targeting NY-ESO-1 for glioblastoma

Everson, Richard; Antonios, Joseph; Lisiero, Dominique N.; Soto, Horacio; Scharnweber, Rudi; Garrett, Matthew C.; Yong, William H.; Li, Ning; Li, Gang; Kruse, Carol A.; Liau, Linda M.; Prins, Robert M.

doi:10.1093/neuonc/nov153

Cited by 35 publications

(23 citation statements)

References 21 publications

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“…Case reports of the abscopal effect (including complete responses) in patients with metastatic melanoma treated with ipilimumab and local radiation therapy (31, 32) have, in part, prompted a number of prospective clinical trials combining immunotherapy and radiation therapy (33). Furthermore, pre-clinical studies suggest that hypomethylating agents may increase tumor antigen exposure (and, more generally, tumor cell visibility), leading to improved response to immune-based therapies (34, 35). These and other pre-clinical and early clinical studies provide initial evidence that chemotherapy or radiation may affect tumor neoantigen load, or trigger an immunogenic cell death through release of damage-associated molecular patterns (such as calreticulin or HMGB1, among others) (36).…”

Section: Understanding Response To Immunotherapymentioning

confidence: 99%

Genomic Approaches to Understanding Response and Resistance to Immunotherapy

Braun

Burke

Allen

2016

Clinical Cancer Research

143

115

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Immunotherapy has led to a paradigm shift in the treatment of some malignancies, providing long-term, durable responses for patients with advanced cancers. However, such therapy has benefited only a subset of patients, with some patients failing to respond to treatment at all, and others achieving a limited response followed by tumor progression. Understanding factors contributing to an effective response and further elucidating mechanisms of resistance will be crucial as these therapies are applied more broadly. Genomics-based approaches have significantly advanced the study of response and resistance to immunotherapy in general, and to immune checkpoint blockade more specifically. Here, we review how genomic and transcriptomic approaches have identified both somatic and germline positive correlates of response, including high mutational / neoantigen load, and low intratumoral heterogeneity, among others. The genomic analysis of resistant tumors has additionally identified crucial factors involved in resistance to immune checkpoint blockade, including loss of PTEN and upregulation of other immune checkpoints. Overall, the continued use of genomic techniques at the point of care, combined with appropriate functional studies, would ideally lead to a better understanding of why certain patients respond to immune-based therapies, allowing clinicians to identify the subset of patients likely to benefit from such therapy, and potentially providing insight into how other therapies may be added in combination to increase the number of patients who may benefit from immunotherapy.

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Section: Understanding Response To Immunotherapymentioning

confidence: 99%

Genomic Approaches to Understanding Response and Resistance to Immunotherapy

Braun

Burke

Allen

2016

Clinical Cancer Research

143

115

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“…Moreover, although the expression of CTAs in human cancer cells is heterogeneous, their expression can be up-regulated by treatment with inhibitors of methylation, such as 5-aza-2Ј-deoxycytidine (Decitabine). Decitabine is a cytosine analog, which inhibits DNA methyltransferases by trapping these enzymes after its incorporation into the DNA, thus reducing methylation of newly synthesized DNA strands (31)(32)(33). Decitabine was shown also to reduce the methylation and to elevate the expression of the MHC class I genes along with different tumor antigens (34 -36).…”

mentioning

confidence: 99%

Human Leukocyte Antigen (HLA) Peptides Derived from Tumor Antigens Induced by Inhibition of DNA Methylation for Development of Drug-facilitated Immunotherapy

Shraibman

Kadosh

Barnea

et al. 2016

Molecular & Cellular Proteomics

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Treatment of cancer cells with anticancer drugs often fails to achieve complete remission. Yet, such drug treatments may induce alteration in the tumor's gene expression patterns, including those of Cancer/Testis Antigens (CTA). The degradation products of such antigens can be presented as HLA peptides on the surface of the tumor cells and be developed into anticancer immunotherapeutics. For example, the DNA methyl transferase inhibitor, 5-aza-2'-deoxycytidine (Decitabine) has limited antitumor efficacy, yet it induces the expression of many genes, including CTAs that are normally silenced in the healthy adult tissues. In this study, the presentation of many new HLA peptides derived from CTAs and induced by Decitabine was demonstrated in three human Glioblastoma cell lines. Such presentation of CTA-derived HLA peptides can be exploited for development of new treatment modalities, combining drug treatment with anti-CTA targeted immunotherapy. The Decitabine-induced HLA peptidomes include many CTAs that are not normally detected in healthy tissues or in cancer cells, unless treated with the drug. In addition, the study included large-scale analyses of the simultaneous effects of Decitabine on the transcriptomes, proteomes and HLA peptidomes of the human Glioblastoma cells. It demonstrates the poor correlations between these three levels of gene expression, both in their total levels and in their response to the drug. The proteomics and HLA peptidomics data are available via ProteomeXchange with identifier PXD003790 and the transcriptomics data are available via GEO with identifier GSE80137.

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“…In addition to this, a clinical trial on multiple myeloma, utilizing ACT with TCRs directed against NY-ESO-1 showed encouraging results such as effective expansion of engineered T cells in vivo, efficient trafficking of T cells to disease site, long-term persistence/continued expression of TCR (for up to 2 years after infusion) and durable target-specific anti-tumor responses without significant safety concerns indicating clinical feasibility of NY-ESO-1 specific ACT for the management of myeloma [95]. Similarly, a pre-clinical study on glioblastoma, utilizing ACT with TCR directed against NY-ESO-1, in combination with Decitabine (DAC) chemotherapy has shown promising results [96]. Study results evidenced that prior administration of DAC to selectively up regulate NY-ESO-1 followed by ACT immunotherapy resulted in an efficient trafficking of NY-ESO-1-specific T cells towards tumor cells leading to survival advantage in mice [96].…”

Section: Current Pre-clinical and Clinical Trials Of Ny-eso-1 Antigenmentioning

confidence: 99%

“…Similarly, a pre-clinical study on glioblastoma, utilizing ACT with TCR directed against NY-ESO-1, in combination with Decitabine (DAC) chemotherapy has shown promising results [96]. Study results evidenced that prior administration of DAC to selectively up regulate NY-ESO-1 followed by ACT immunotherapy resulted in an efficient trafficking of NY-ESO-1-specific T cells towards tumor cells leading to survival advantage in mice [96]. Furthermore, phase I trial on chemo-immunotherapy, has been performed on relapsed/refractory solid tumors including Ewing's sarcoma, osteosarcoma and rhabdomyosarcoma [97].…”

Section: Current Pre-clinical and Clinical Trials Of Ny-eso-1 Antigenmentioning

confidence: 99%

Unleashing the immune response to NY-ESO-1 cancer testis antigen as a potential target for cancer immunotherapy

et al. 2020

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Introduction: Cancer Immunotherapy has recently emerged as a promising and effective modality to treat different malignancies. Antigenic profiling of cancer tissues and determination of any pre-existing immune responses to cancer antigens may help predict responses to immune intervention in cancer. NY-ESO-1, a cancer testis antigen is the most immunogenic antigen to date. The promise of NY-ESO-1 as a candidate for specific immune recognition of cancer comes from its restricted expression in normal adult tissue but frequent occurrence in multiple tumors including melanoma and carcinomas of lung, esophageal, liver, gastric, prostrate, ovarian, and bladder. Main body: This review summarizes current knowledge of NY-ESO-1 as efficient biomarker and target of immunotherapy. It also addresses limitations and challenges preventing a robust immune response to NY-ESO-1 expressing cancers, and describes pre-clinical and clinical observations relevant to NY-ESO-1 immunity, holding potential therapeutic relevance for cancer treatment. Conclusion: NY-ESO-1 induces strong immune responses in cancer patients but has limited objective clinical responses to NY-ESO-1 expressing tumors due to effect of competitive negative signaling from immune-checkpoints and immune-suppressive tumor microenvironment. We propose that combination therapy to increase the efficacy of NY-ESO-1 specific immunotherapeutic interventions should be explored to unleash the immune response against NY-ESO-1 expressing tumors.

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Efficacy of systemic adoptive transfer immunotherapy targeting NY-ESO-1 for glioblastoma

Abstract: These results reveal an innovative, clinically feasible strategy for the treatment of glioblastoma.

Cited by 35 publications

References 21 publications

Genomic Approaches to Understanding Response and Resistance to Immunotherapy

Genomic Approaches to Understanding Response and Resistance to Immunotherapy

Human Leukocyte Antigen (HLA) Peptides Derived from Tumor Antigens Induced by Inhibition of DNA Methylation for Development of Drug-facilitated Immunotherapy

Unleashing the immune response to NY-ESO-1 cancer testis antigen as a potential target for cancer immunotherapy

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