PD-L1 x 4-1BB (CD137) Bispecific Antibody Pipeline Review

PD-L1 x 4-1BB (CD137) Bispecific Antibody Pipeline Review

Target 1: Programmed death-ligand 1 (PD-L1); CD274; B7-H1

Target 2: 4-1BB; CD137; TNFRSF9

Product Category: Antibody

This product provides basic pipeline information on investigational bispecific antibodies targeting PD-L1 and 4-1BB.

This product consists of:

• Competitors described in a tabular format covering drug code/INN, target(s)/MoA, class of compound, product category, indication(s) & R&D stage.
• Project History with links to source of information (press release, homepage, abstracts, presentations, annual reports etc).
• One-month online access to La Merie Publishing’s database for investigational therapies targeting PD-L1 and 4-1BB (prerequisite: access to internet).

This product is delivered on the very same day of purchase by e-mail containing competitor and project history reports in pdf format and database credentials. Reports are prepared on the same day.

4-1BB (CD137, TNFRSF9) is a costimulatory receptor of the TNF receptor superfamily (TNFRSF) and accumulates on the T-cell surface upon activation. Receptor stimulation by endogenous 4-1BB ligand (4-1BBL) or agonistic 4-1BB antibodies can markedly augment T-cell activation and upregulate inflammatory cytokine response. Agonistic 4-1BB antibodies have exhibited potent anticancer efficacy in a variety of syngeneic mouse models. However, the on-target-off-tumor liver toxicity has hampered the successful clinical development of therapeutic 4-1BB agonists.

Programmed death-ligand 1 (PD-L1) also known as CD274 or B7 homolog 1 (B7-H1) is a a 40kDa type 1 transmembrane protein playing a major role in suppressing the adaptive arm of immune systems during particular events. The binding of PD-L1 to the inhibitory checkpoint molecule PD-1 transmits an inhibitory signal which reduces the proliferation of antigen-specific T-cells in lymph nodes, while simultaneously reducing apoptosis in regulatory T cells. PD-L1 is expressed on both hematopoietic and nonhematopoietic cells in tissues. PD-L1 is shown to be highly expressed in a variety of malignancies, particularly lung cancer.

One of the most promising next-generation 4-1BB targeting strategies is the use of bispecific antibodies (BsAb) or bispecific fusion proteins, which are designed to be enriched in the tumor microenvironment (TME) enabling tumor cell–mediated 4-1BB activation, thereby minimizing on-target-off-tumor toxicity. Typically, such bispecific proteins are composed of a tumor-associated antigen (TAA)-recognizing arm and a 4-1BB–agonistic arm.

A number of PD-L1 x 4-1BB bispecific antibodies are in preclinical and clinical development which were designed to elicit an antitumor response via conditional activation of 4-1BB on T cells and natural killer (NK) cells, which is strictly dependent on simultaneous binding of the PD-L1 arm.