PD-L1 and 4-1BB (CD137): promising immuno-oncology therapy combination to overcome on-target-off-tumor toxicity – a pipeline review

STUTTGART, Germany I September 24, 2025 I La Merie Publishing announced the release of its newest product offering reviewing the pipeline of active therapy candidates in research and development targeting CD47 or SIRPα: 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.

The report “Pipeline of PD-L1 x 4-1BB (CD137) Bispecific Antibodies” can be acquired at La Merie Publishing’s online store: https://lamerie.com/report/pipeline-of-pd-l1-x-4-1bb-cd137-bispecific-antibodies/

About La Merie Publishing

La Merie Publishing is an independent business information provider for the biotechnology and pharmaceutical industry. La Merie Publishing prepares brief and full reports. La Merie Publishing products can be purchased in the online store www.lamerie.com and from selected Resellers.

La Merie Publishing offers the service of custom report preparation for corporate clients, including, but not limited to, customized reports about target evaluation, pipeline analysis, technology assessments, drug and competitor profiles, partnering and business deal terms and any other competitive intelligence elaboration of interest.

Among La Merie Publishing’s services are the pre-scoped evaluation of customer-selected targets for drug discovery: Target Evaluation for Drug Discovery: Pre-Scoped Premium Evaluation and the pre-scoped review of the pipeline of immunotherapies against customer-selected targets: Pipeline Review of Customer-Selected Targeted Immunotherapies: Pre-Scoped Competitor Analysis.

SOURCE: La Merie Publishing