NI-3201 Is a Bispecific Antibody Mediating PD-L1-Dependent CD28 Co-stimulation on T Cells for Enhanced Tumor Control.

Despite advances in cancer immunotherapy, such as targeting the PD-1/PD-L1 axis, a substantial number of patients harbor tumors that are resistant or relapse. Selective engagement of T-cell co-stimulatory molecules with bispecific antibodies may offer novel therapeutic options by enhancing signal 1-driven activation occurring via T-cell receptor engagement. In this study, we report the development and preclinical characterization of NI-3201, a PD-L1×CD28 bispecific antibody generated on the κλ-body platform that was designed to promote T-cell activity and antitumor function through a dual mechanism of action.

Targeting CEACAM5-positive solid tumors using NILK-2401, a novel CEACAM5xCD47 κλ bispecific antibody.

Background: Blocking the CD47 "don't eat me"-signal on tumor cells with monoclonal antibodies or fusion proteins has shown limited clinical activity in hematologic malignancies and solid tumors thus far. Main side effects are associated with non-tumor targeted binding to CD47 particularly on blood cells.

Methods: We present here the generation and preclinical development of NILK-2401, a CEACAM5×CD47 bispecific antibody (BsAb) composed of a common heavy chain and two different light chains, one kappa and one lambda, determining specificity (so-called κλ body format).