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Adoptive therapy with TCR gene-engineered T cells to treat patients with MAGE-C2-positive melanoma and head and neck cancer

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Background & Aim We are scheduling a patient study, in which we will target the Cancer Germline Antigen MAGE-C2 (MC2), and use T cells with a young phenotype. MC2 is… Click to show full abstract

Background & Aim We are scheduling a patient study, in which we will target the Cancer Germline Antigen MAGE-C2 (MC2), and use T cells with a young phenotype. MC2 is highly expressed in, amongst others, melanoma, head-and-neck squamous cell carcinoma (HNSSC), bladder, and triple-negative breast cancers but not in healthy adult tissues. Methods, Results & Conclusion We isolated MC2-specific TCRs from melanoma patients who showed clinical responses following vaccination that were accompanied by significant frequencies of anti-MC2 CD8 T cells in blood and tumor without apparent side effects. Following extensive evaluation of in vitro anti-tumor and self-reactivities, we have selected a TCR that recognizes the ALK epitope in the context of HLA-A2 for clinical development. Furthermore our preclinical studies showed that epigenetic pretreatment of tumor cells, but not normal cells, up-regulated MC2 gene expression and resulted in enhanced recognition of MC2 by the selected TCR. In parallel to the above studies, we renewed our GMP protocol to process T cells, using stimulating antibodies and cytokines, to generate T cells with a young phenotype. In a phase I/II study, we will explore the safety and anti-tumor efficacy of T cells engineered with the selected TCR in patients with MC2-positive melanoma and HNSSC. The study contains the following unique elements: - CT antigen not targeted before by T cell therapy - a new T cell processing method to generate young T cells - pretreatment of patients with epigenetic drugs to increase MC2 expression in the tumor - no chemotherapy prior to T cell infusion. All preparations have been successfully completed - including production and testing of the clinical vector batch and the clinical scale process validations. To date regulatory approvals have been obtained - including license for use of the vector and approval for the clinical trial. Patient treatment will start Q1 2020.

Keywords: melanoma; melanoma head; tcr; positive melanoma; head neck; tumor

Journal Title: Cytotherapy
Year Published: 2020

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