The potential of the CMB305 vaccine regimen to target NY-ESO-1 and improve outcomes for synovial sarcoma and myxoid/round cell liposarcoma patients

Pollack, Seth M.

doi:10.1080/14760584.2018.1419068

Cited by 36 publications

(32 citation statements)

References 73 publications

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“…This data was the basis of further development of the vaccine based on NY-ESO1-activated DCs by transduction with a lentiviral vector. Such a vaccine has demonstrated high immunological efficiency in patients with refractory synovial sarcoma [36]. Accordingly, in the study by Jura et al [23], immunohistochemically, NY-ESO1, PRAME, MAGEA4, and MAGEA1…”

Section: Discussionmentioning

confidence: 99%

Cancer/testis antigens expression during cultivation of melanoma and soft tissue sarcoma cells

Данилова¹,

Misyurin

Novik³

et al. 2020

Clin Sarcoma Res

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Background: Autologous dendritic cells (DC) loaded with tumor-associated antigens (TAAs) are a promising approach for anticancer immunotherapy. Polyantigen lysates appear to be an excellent source of TAAs for loading onto the patient's dendritic cells. Cancer/testis antigens (CTA) are expressed by a wide range of tumors, but are minimally expressed on normal tissues, and could serve as a universal target for immunotherapy. However, CTA expression levels can vary significantly in patients with the same tumor type. We proposed that patients who do not respond to DC-based therapy may have distinct features of the CTA expression profile on tumor cells. Patients and methods: We compared the gene expression of the principal families CTA in 22 melanoma and 27 soft tissue and bone sarcomas cell lines (STBS), received from patients and used for DC vaccine preparation. Results: The majority (47 of 49, 95.9%) cell lines showed CTA gene activity. The incidence of gene expression of GAGE, NYESO1, MAGEA1, PRAME's was significantly different (adj. p < 0.05) between melanoma and sarcoma cell lines. The expression of the SCP1 gene was detected neither in melanoma cells nor in the STBS cells. Clustering by the gene expression profile revealed four different expression patterns. We found three main patterns types: hyperexpression of multiple CTA, hyperexpression of one CTA with almost no expression of others, and no expression of CTA. All clusters types exist in melanoma and sarcoma cell lines. We observed dependence of killing efficacy from the PRAME (rho = 0.940, adj. p < 0.01) expression during real-time monitoring with the xCELLigence system of the interaction between melanoma or sarcoma cells with the T-lymphocytes activated by the lysate of selected allogenous melanoma cell lines with high expression of CTA. Conclusion: Our results demonstrate that one can use lysates from allogeneic melanoma cell lines as a source of CTA for DC load during the production of anticancer vaccines for the STBS treatment. Patterns of CTA expression should be evaluated as biomarkers of response in prospective clinical trials.

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Section: Discussionmentioning

confidence: 99%

Cancer/testis antigens expression during cultivation of melanoma and soft tissue sarcoma cells

Данилова¹,

Misyurin

Novik³

et al. 2020

Clin Sarcoma Res

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“…LV305, was found to selectively induce NY-ESO-1 specific expression in dendritic cells and promoting tumor responses in patients [87]. Similarly, phase 1 study in synovial and myxoid round cell liposarcoma with CMB305 vaccine containing LV305 was shown to prime NY-ESO-1 specific T cell responses leading to enhanced overall survival [88]. Monoclonal antibodies (mAbs) against tumor-associated antigens have also shown promising results.…”

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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“…NILVs have also been utilised as vectors of choice for cancer immunotherapy [ 75 , 78 , 88 , 93 , 94 , 95 , 96 ]. These vectors have been successfully used to deliver immunogens to dendritic cells, professional antigen presenting cells that can directly prime CD8+ T cell responses.…”

Section: Old and Current Applications Of Nilvsmentioning

confidence: 99%

The Old and the New: Prospects for Non-Integrating Lentiviral Vector Technology

Apolonia

2020

Viruses

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Lentiviral vectors have been developed and used in multiple gene and cell therapy applications. One of their main advantages over other vectors is the ability to integrate the genetic material into the genome of the host. However, this can also be a disadvantage as it may lead to insertional mutagenesis. To address this, non-integrating lentiviral vectors (NILVs) were developed. To generate NILVs, it is possible to introduce mutations in the viral enzyme integrase and/or mutations on the viral DNA recognised by integrase (the attachment sites). NILVs are able to stably express transgenes from episomal DNA in non-dividing cells or transiently if the target cells divide. It has been shown that these vectors are able to transduce multiple cell types and tissues. These characteristics make NILVs ideal vectors to use in vaccination and immunotherapies, among other applications. They also open future prospects for NILVs as tools for the delivery of CRISPR/Cas9 components, a recent revolutionary technology now widely used for gene editing and repair.

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The potential of the CMB305 vaccine regimen to target NY-ESO-1 and improve outcomes for synovial sarcoma and myxoid/round cell liposarcoma patients

Cited by 36 publications

References 73 publications

Cancer/testis antigens expression during cultivation of melanoma and soft tissue sarcoma cells

Cancer/testis antigens expression during cultivation of melanoma and soft tissue sarcoma cells

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

The Old and the New: Prospects for Non-Integrating Lentiviral Vector Technology

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