Pipeline of PD-L1 x 4-1BB (CD137) Bispecific Antibodies

This competitive intelligence report about PD-L1 x 4-1BB (CD137) Bispecific Antibodies provides an up-to-date competitor evaluation in the field of emerging therapy candidates in research and development targeting simultaneously PD-L1 and 4-1BB (CD137). This report will be prepared on demand within one working day upon order placement. The report lists active PD-L1 x 4-1BB targeted R&D programs by R&D phase in a tabular format and describes in brief the profile of PD-L1 x 4-1BB bispecific antibodies by drug modality. The report will be provided in pdf format and sent by e-mail to the customer.

As an example of this category of on demand reports, please see our free sample report of “Pipeline of 5T4-Targeted Immunotherapies”.

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.