autologous NY-ESO-1/LAGE-1a-specific HLA-A*02:01-restricted TCR-expressing T lymphocytes MDG1015

A preparation of autologous T lymphocytes that have been genetically engineered to express a T-cell receptor (TCR) specific for the human leukocyte antigen (HLA)-A*02:01-restricted cancer-testis antigens (CTAs) NY-ESO-1 and L antigen family member 1 isoform A (LAGE-1A; LAGE-A1; CT6.2a), and a programmed cell death protein 1 (PD-1; PDCD1; CD279)-4-1BB (CD137; tumor necrosis factor receptor superfamily member 9; TNFRSF9) costimulatory switch protein (CSP), with potential immunomodulating and antineoplastic activities. Upon reintroduction into the patient, autologous NY-ESO-1/LAGE-1a-specific HLA-A*02:01-restricted TCR-expressing T lymphocytes MDG1015 specifically targets and binds to NY-ESO-1 and/or LAGE-1A expressed on tumor cells. This may lead to cytotoxic T-lymphocyte (CTL)-mediated elimination of tumor cells expressing NY-ESO-1 and/or LAGE-1A. In addition, upon binding of the TCR-T cells MDG1015 to NY-ESO-1 and/or LAGE-1A expressed on tumor cells, the PD-1-4-1BB CSP is activated. This abrogates PD-1-mediated signaling in T cells and PD-1-mediated T-cell inhibition, and activates 4-1BB signaling locally in the tumor microenvironment (TME), which enhances the activity and persistence of the TCR-T cells MDG1015. NY-ESO-1 and LAGE-1A, members of the CTA family, are overexpressed on the surface of various tumor cell types; they share a specific HLA-A*02:01 epitope, 157-165, which is expressed on certain tumor cell types while its expression is not found on normal, healthy cells.