11 Oct Novel Immune Checkpoint Inhibitor Has Potential Against Variety of Tumors
MedicalResearch.com Interview with:
Bernard Vanhove, Chief Operating Officer
Director of R&D and International Scientific Collaborations
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Myeloid suppressive cells, including tumor associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC), represent an abundant immune cell type in the microenvironment of solid tumors where they promote tumor growth, metastases, angiogenesis, inhibiting anti-tumor immune responses. Myeloid cells selectively express SIRPα, an immune tyrosine associated inhibitory receptor (also named CD172a), which controls myeloid functions.
We investigated the role of Effi-DEM, new generation checkpoint inhibitor specifically targeting the SIRP- α receptor on the strategic SIRP-α/CD47 pathway in human macrophages polarization and MDSC differentiation. CD47 the ligand of SIRP alpha is ubiquitously expressed in human cells and has been found to be overexpressed in many different tumor cells with a poor prognosis established. Effi-DEM is a selective antagonist of these myeloid suppressive cells as its target SIRP-α is expressed on these cells. Based on this rationale, the preclinical studies conducted with Effi-DEM have demonstrated its potential to transform suppressor myeloid and tumor associated macrophage cells in non-suppressive cells, thereby inducing a reactivation of the immune response. Effi-DEM has also shown to be effective in various aggressive cancer models with encouraging preclinical results, both in monotherapy and in therapeutic combinations with anti-PD-L1 (checkpoint inhibitors) and anti-CD137 (4-1BB) mAbs, activators of the T-cell response. Significant efficacy and survival increase data were demonstrated in models of hepatocarcinoma, melanoma and triple negative breast cancer.
MedicalResearch.com: What should readers take away from your report?
Response: Our findings suggest that SIRPα is a novel immune checkpoint that controls an important population of suppressive myeloid cells through macrophage polarization and wiping away immune suppressive capacities of MDSC, transforming these cells in effectors cells. Targeting selectively on the strategic SIRP-α/CD47 pathway, Effi-DEM has the potential to modify the suppressive tumor micro-environment and to potentiate anti-tumor immune responses in vivo. It has also been shown to be effective in various cancer models, with results both in monotherapy and in immune therapeutic combination, for which we have demonstrated a synergy, and therefore meets current clinical needs
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: The relevant and strong data generated by these preclinical advances have reinforced the rationale for further clinical development of Effi-DEM in various cancers.
MedicalResearch.com: Is there anything else you would like to add?
Response: The preclinical steps achieved so far have validated the innovation and therapeutic potential of our new generation proprietary checkpoint inhibitor, and show how the product enhances immune response by targeting selectively novel checkpoint SIRP-α. OSE Immunotherapeutics is at the forefront of this new immuno-oncology area and is determined to make of Effi-DEM a first-in-class treatment.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Annual World Gene Convention-2016 abstract
Selective Targeting of The SIRP-α Immune Checkpoint To Dampen Suppression By Myeloïd-Derived Suppressor Cells And Control Polarization Of Human Macrophages
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