Definition

A human bispecific antibody composed of a single-chain variable fragment (scFv) domain targeting the immune co-stimulatory receptor 4-1BB (CD137; tumor necrosis factor receptor superfamily member 9; TNFRSF9) and a scFv domain targeting the tumor associated antigen (TAA) 5T4 (trophoblast glycoprotein; TPBG), that are linked through a mutated and silenced immunoglobulin G (IgG)-Fc domain, with potential immunomodulatory and antineoplastic activities. Upon administration of anti-4-1BB/5T4 bispecific antibody ALG.APV-527, the anti-5T4-specific scFv domain of ALG.APV-527 targets and binds to 5T4 expressed on tumor cells and the anti-4-1BB-specific scFv domain targets and binds to 4-1BB expressed on certain immune cells, such as T cells and natural killer cells (NK) cells within the tumor microenvironment (TME). This crosslinks T cells and tumor cells and allows for conditional 4-1BB activation, which stimulates the activation and proliferation of NKs and cytotoxic T lymphocytes (CTLs) in the TME leading to an anti-tumor immune response against the 5T4-expressing tumor cells. 5T4 is expressed on many different tumor cell types, including tumor-initiating cells, but expressed at low levels or not at all in normal tissue. ALG.APV-527 minimizes systemic immune activation and allows for tumor-specific responses that are localized to 5T4-positive tumors.