Definition

A preparation of off-the-shelf (OTS) donor-derived T lymphocytes that are reactive to multiple tumor-associated antigens (TAAs), with potential immunomodulating and antineoplastic activities. T cells derived from allogeneic donor leukocytes are stimulated with monocyte-derived dendritic cells (DCs) that are pulsed with a mix of peptides derived from the three TAAs Wilms tumor 1 (WT1), preferentially expressed antigen of melanoma (PRAME; melanoma antigen preferentially expressed in tumors; Opa-interacting protein 4; OIP-4) and survivin (baculoviral IAP repeat-containing protein 5; BIRC5). The antigen-specific T-cells are subsequently expanded. Upon administration of WT1/PRAME/survivin-specific T-cells MANA 312, the T cells recognize, induce a T-cell mediated immune response in and induce lysis of tumor cells that express WT1, PRAME and/or survivin. In addition, tumor cell lysis induces the release of a broader set of tumor antigens, thereby further stimulating the immune system to exert an anti-tumor T-cell-mediated immune response. WT1, PRAME and survivin, overexpressed in a variety of tumor cell types, play key roles in tumor cell proliferation.