Method of treating tumor growth and metastasis by using trifunctional antibodies to reduce the risk for graft-versus-host disease in allogeneic antitumor cell therapy

Abstract

The patent claims that trifunctional (TrFAb) and trispecific antibodies (TrSAb) will redirect immune effectors to tumor associated antigens (TAAs) while downregulating allo-activation of donor T cells, leading to reduced graft- versus-host disease (GvHD). A TrFAb is a bispecific antibody (BiAb) that binds to immune effector cells and targets a TAA, whilst binding of the Fc-portion of the TrFAb to Fcγ receptors (FcγR) on immune effector cells leads to downregulation of allo-activation of donor T cells responsible for mediating GvHD. Furthermore, a TrSAb consists of a proposed construct that binds to immune effectors and to two separate TAAs while the Fc-portion of the TrSAb constructs interacts to downregulate allo-activation as proposed in the TrFAb construct. The patent claims that infusion of TrFAb or TrSAb would markedly improve antitumor activity whilst maintaining potent anti-GvHD activity when used after allogeneic stem cell transplantation for both hematologic malignancies and solid tumors.