First-in-Class, First-in-Human Study Evaluating LV305, a Dendritic-Cell Tropic Lentiviral Vector, in Sarcoma and Other Solid Tumors Expressing NY-ESO-1

Somaiah, Neeta; Block, Matthew S.; Kim, Joseph W.; Shapiro, Geoffrey I.; Khanh, T.; Hwu, Patrick; Eder, Joseph P.; Jones, Robin L.; Lu, Hailing; Meulen, Jan ter; Bohac, Chet; Chen, Michael; Hsu, Frank J.; Gnjatic, Sacha; Pollack, Seth M.

doi:10.1158/1078-0432.ccr-19-1025

Cited by 75 publications

(56 citation statements)

References 24 publications

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“…In ESCC, mature LAMP3 + DCs has been reportedly associated with increasing tumor‐infiltrating CD8 + T cells 58 . Recently, promising findings of a phase I study on LV305, an engineered harmless virus targeting DCs, have been released 59 . LV305 upregulated the expression level of the New York ESCC‐1 (NY‐ESO‐1) cancer testis antigen in DCs, promoting immune responses against NY‐ESO‐1‐expressing tumors 60 .…”

Section: Dendritic Cellsmentioning

confidence: 99%

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Tumor immune microenvironment and immune checkpoint inhibitors in esophageal squamous cell carcinoma

et al. 2020

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Esophageal squamous cell carcinoma (ESCC) is the main prevalent histological type of esophageal cancer, predominantly constituting 90% of cases worldwide. Despite the development of multidisciplinary therapeutic approaches, its prognosis remains unfavorable. Recently, the development of monoclonal antibodies inhibiting programmed death 1 (PD‐1) or programmed death‐ligand 1 (PD‐L1) has led to marked therapeutic responses among multiple malignancies including ESCC. However, only a few patients achieved clinical benefits due to resistance. Therefore, precise and accurate predictive biomarkers should be identified for personalized immunotherapy in clinical settings. Because the tumor immune microenvironment can potentially influence the patient's response to immune checkpoint inhibitors, tumor immunity, such as PD‐L1 expression on tumors, tumor‐infiltrating lymphocytes, tumor‐associated macrophages, and myeloid‐derived suppressor cells, in ESCC should be further investigated. In this review, accumulated evidence regarding the tumor immune microenvironment and immune checkpoint inhibitors in ESCC are summarized.

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Section: Dendritic Cellsmentioning

confidence: 99%

“…All treatment‐related AEs were grade 1 or 2. The disease control rate was 56% in all patients 59 . Further investigation of LV305 is continuously explored, possibly in combination with a boosting vaccine and/or other agents, such as immune checkpoint inhibitors.…”

Section: Dendritic Cellsmentioning

confidence: 99%

Tumor immune microenvironment and immune checkpoint inhibitors in esophageal squamous cell carcinoma

et al. 2020

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“…The above-mentioned lentiviral vectors have been tested in cancer patients with different solid NY-ESO-1-expressing tumors [45]. In this phase I clinical trial, so-called LV305 was assessed (Table S1 (Supplementary Materials)), which represents the so-called ZVex, a third generation lentiviral-based Sindbis virus glycoprotein functionalized vector, which is replication-incompetent and integration-deficient to reduce lentiviral-related side effects [94].…”

Section: Dc-sign Receptor Targetingmentioning

confidence: 99%

Dendritic Cells in Anticancer Vaccination: Rationale for Ex Vivo Loading or In Vivo Targeting

Baldin

Savvateeva

Bazhin

et al. 2020

Cancers

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Dendritic cells (DCs) have shown great potential as a component or target in the landscape of cancer immunotherapy. Different in vivo and ex vivo strategies of DC vaccine generation with different outcomes have been proposed. Numerous clinical trials have demonstrated their efficacy and safety in cancer patients. However, there is no consensus regarding which DC-based vaccine generation method is preferable. A problem of result comparison between trials in which different DC-loading or -targeting approaches have been applied remains. The employment of different DC generation and maturation methods, antigens and administration routes from trial to trial also limits the objective comparison of DC vaccines. In the present review, we discuss different methods of DC vaccine generation. We conclude that standardized trial designs, treatment settings and outcome assessment criteria will help to determine which DC vaccine generation approach should be applied in certain cancer cases. This will result in a reduction in alternatives in the selection of preferable DC-based vaccine tactics in patient. Moreover, it has become clear that the application of a DC vaccine alone is not sufficient and combination immunotherapy with recent advances, such as immune checkpoint inhibitors, should be employed to achieve a better clinical response and outcome.

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“…Following the success of preclinical studies, recent phase 1 vaccination trial evaluating LV305 in NY-ESO-1 expressing solid tumors also showed promising results. 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].…”

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

confidence: 98%

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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First-in-Class, First-in-Human Study Evaluating LV305, a Dendritic-Cell Tropic Lentiviral Vector, in Sarcoma and Other Solid Tumors Expressing NY-ESO-1

Cited by 75 publications

References 24 publications

Tumor immune microenvironment and immune checkpoint inhibitors in esophageal squamous cell carcinoma

Tumor immune microenvironment and immune checkpoint inhibitors in esophageal squamous cell carcinoma

Dendritic Cells in Anticancer Vaccination: Rationale for Ex Vivo Loading or In Vivo Targeting

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

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