Translational analysis from SCALOP trial: CCL5 as a prognostic biomarker and a potentially actionable target in locally advanced pancreatic cancer (LAPC).

Mukherjee, Somnath; Lanfredini, Simone; Cox, Catrin; Thapa, Asmita; Hughes, Sophie; Bangs, Fiona; Willenbrock, Frances; Wilhelm-Benartzi, Charlotte S.; Abraham, Aswin George; Owens, Robert; Sabbagh, Ahmad Al; Maughan, Tim; Hurt, Chris; O’Neill, Eric

doi:10.1200/jco.2020.38.4_suppl.740

Cited by 2 publications

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“…The authors hypothesize that a CCL5 inhibitor in combination with anti-PD-1 could overcome resistance to treatment. One last example, the translational analysis results from the SCALOP multi-center phase II trial were presented at the ASCO Conference this year (Mukherjee et al, 2020). The study by Zhang et al provided a ranking of the sensitivity of human cancers to anti-CTLA-4 antibodies.…”

Section: Fsfc Contributions To Cancer Immunotherapy Researchmentioning

confidence: 99%

Full Spectrum Flow Cytometry as a Powerful Technology for Cancer Immunotherapy Research

Bonilla¹,

Reinin²,

Chua³

2021

Front. Mol. Biosci.

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The Nobel Prize-deserving concept of blocking inhibitory pathways in T cells, to unleash their anti-tumoral capacity, became one of the pillars of cancer treatment in the last decade and has resulted in durable clinical responses for multiple cancer types. Currently, two of the most important goals in cancer immunotherapy are to understand the mechanisms resulting in failure to checkpoint blockade and to identify predictive immunological biomarkers that correlate to treatment response, disease progression or adverse effects. The identification and validation of biomarkers for routine clinical use is not only critical to monitor disease or treatment progression, but also to personalize and develop new therapies. To achieve these goals, powerful research tools are needed. Flow cytometry stands as one of the most successful single-cell analytical tools used to characterize immune cell phenotypes to monitor solid tumors, hematological malignancies, minimal residual disease or metastatic progression. This technology has been fundamental in diagnosis, treatment and translational research in cancer clinical trials. Most recently, the need to evaluate simultaneously more features in each cell has pushed the field to implement more powerful adaptations beyond conventional flow cytometry, including Full Spectrum Flow Cytometry (FSFC). FSFC captures the full emission spectrum of fluorescent molecules using arrays of highly sensitive light detectors, and to date has enabled characterization of 40 parameters in a single sample. We will summarize the contributions of this technology to the advancement of research in immunotherapy studies and discuss best practices to obtain reliable, robust and reproducible FSFC results.

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Section: Fsfc Contributions To Cancer Immunotherapy Researchmentioning

confidence: 99%

Full Spectrum Flow Cytometry as a Powerful Technology for Cancer Immunotherapy Research

Bonilla¹,

Reinin²,

Chua³

2021

Front. Mol. Biosci.

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Biomarker analysis of VT1021, a first-in-class therapeutic agent that stimulates Thrombospondin-1 and reprograms the tumor microenvironment

Chen¹,

Vincent²,

Li³

et al. 2023

Preprint

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VT1021 is a first-in-class therapeutic agent which has been tested in a phase I/II clinical study in solid tumors (NCT03364400) and has advanced to a phase II/III clinical study in glioblastoma (NCT03970447). Preclinical studies demonstrated that VT1021 inhibited tumor growth via stimulation of thrombospondin-1 (TSP-1) and reprogramming the tumor microenvironment. We sought to confirm the mechanism of action (MOA) of VT1021 in a clinical setting and identify biomarkers for VT1021 in future clinical studies. Accordingly, we evaluated potential biomarkers from peripheral blood samples and available paired biopsy samples from evaluable subjects enrolled in the phase I/II expansion study. Here, we report the clinical confirmation of TSP-1 induction by VT1021 in peripheral blood and tumor biopsy samples. Moreover, we observed that treatment with VT1021 resulted in the remodeling of the TME from one that was immunosuppressive and tumor-promoting to one that is immune active and tumor-inhibiting. The modifications were characterized by an increased ratio of CD8+ T cells (cytotoxic T lymphocytes, or CTLs) to T Regulatory (Treg) cells, increased Tumor-infiltrating lymphocytes (TIL), decreased T cell exhaustion, increased M1:M2 macrophage ratio and decreased microvascular density. To identify non-invasive biomarkers for VT1021, we analyzed plasmatic cytokines and identified four cytokines as potential predictive biomarkers for VT1021 activity, including matrix metallopeptidase 9 (MMP9), plasminogen activator inhibitor-1 (PAI-1), chitinase 3 like protein 1 (CHI3L1), and C-C Motif Chemokine Ligand 5 (CCL5). In addition, we found that macrophage migration inhibitory factor (MIF), Interleukin-18 binding protein alpha (IL-18 Bpa), CHI3L and CCL5 could be potential pharmacodynamic biomarkers for VT1021.

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Translational analysis from SCALOP trial: CCL5 as a prognostic biomarker and a potentially actionable target in locally advanced pancreatic cancer (LAPC).

Cited by 2 publications

References 0 publications

Full Spectrum Flow Cytometry as a Powerful Technology for Cancer Immunotherapy Research

Full Spectrum Flow Cytometry as a Powerful Technology for Cancer Immunotherapy Research

Biomarker analysis of VT1021, a first-in-class therapeutic agent that stimulates Thrombospondin-1 and reprograms the tumor microenvironment

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