CD87-targeted BiTE and CAR-T cells potently inhibit invasive nonfunctional pituitary adenomas

Recently,bispecific T-cell engagers(BiTEs)and chimeric antigen receptor-modified T cells(CAR-Ts)have been shown to have high therapeutic efficacy in hematological tumors.CD87 is highly expressed in solid tumors with an oncogenic function.To assess their cytotoxic effects on invasive nonfunctioning pituitary adenomas(iNFPAs),we first examined CD87 expression and its effects on the metabolism of iNFPA cells.We generated CD87-specific BiTE and CAR/IL-12 T cells,and their cytotoxic effects on iNFPAs cells and in mouse models were determined.CD87 had high expression in i NFPA tissue and cell samples but was undetected in noncancerous brain samples.CD87×CD3 BiTE and CD87 CAR/IL-12 T-cells showed antigenic specificity and exerted satisfactory cytotoxic effects,decreasing tumor cell proliferation in vitro and reducing existing tumors in experimental mice.Overall,the above findings suggest that CD87 is a promising target for the immunotherapeutic management of iNFPAs using anti-CD87 BiTE and CD87-specific CAR/IL-12 T cells.

Characterization of a novel bispecific antibody targeting tissue factor-positive tumors with T cell engagement

T cell engaging bispecific antibody(TCB)is an effective immunotherapy for cancer treatment.Through co-targeting CD3 and tumor-associated antigen(TAA),TCB can redirect CD3+T cells to eliminate tumor cells regardless of the specificity of T cell receptor.Tissue factor(TF)is a TAA that involved in tumor progression.Here,we designed and characterized a novel TCB targeting TF(TF-TCB)for the treatment of TF-positive tumors.In vitro,robust T cell activation,tumor cell lysis and T cell proliferation were induced by TF-TCB.The tumor cell lysis activity was dependent upon both CD3 and TF binding moieties of the TF-TCB,and was related to TF expression level of tumor cells.In vivo,in both tumor cell/human peripheral blood mononuclear cells(PBMC)co-grafting model and established tumor models with poor T cell infiltration,tumor growth was strongly inhibited by TF-TCB.T cell infiltration into tumors was induced during the treatment.Furthermore,efficacy of TF-TCB was further improved by combination with immune checkpoint inhibitors.For the first time,our results validated the feasibility of using TF as a target for TCB and highlighted the potential for TF-TCB to demonstrate efficacy in solid tumor treatment.