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Updated: May 16, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
[Bispecific antibodies in prostate cancer therapy]
Susanne Jung1, Jonas Heitmann1, Martin Pflügler1
1KKE Translationale Immunologie, Universitätsklinikum Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Deutschland.
Abstract:
Prostate cancer (PC) is the second most common cancer in men. As soon as androgen deprivation therapy fails, treatment options are limited. Despite intense efforts, hardly any of the T cell-based immunotherapeutic strategies that have revolutionized oncological treatment in other cancer entities are yet established for the treatment of PC. This includes immune checkpoint inhibition, which generally reinforces T cell-immunity but failed to achieve broad activity in PC, as well as chimeric antigen receptor T (CART) cells and bispecific antibodies (bsAbs), which specifically mobilize T cells against tumor cells. Compared to CART cells, bsAbs have the advantage of being readily available "off-the-shelf" reagents. Currently several bispecific constructs are in development for PC. While development of some was discontinued due to substantial side effects or development of anti-drug antibodies, others have yielded promising results. These include in particular bsAbs directed against six-transmembrane epithelial antigen of the prostate 1 (STEAP1) and prostate-specific membrane antigen (PSMA), which are currently being evaluated in both patients with metastasized disease and biochemical relapse. The concepts underlying the different constructs, the current status of clinical development, and future perspectives are discussed.
Insights
Prostate cancer treatments are limited after hormone therapy failure. Bispecific antibodies (bsAbs) show promise, offering an off-the-shelf option by directing T cells against cancer cells, unlike other immunotherapies.
Area of Science:
- Oncology
- Immunotherapy
- Prostate Cancer Research
Context:
- Prostate cancer (PC) is a leading cancer in men with limited options post-androgen deprivation therapy.
- T cell-based immunotherapies have revolutionized other cancers but show limited success in PC.
- Existing immunotherapies like checkpoint inhibitors have not broadly impacted PC treatment.
Purpose:
- To review the current landscape of T cell-mobilizing immunotherapies for prostate cancer.
- To compare bispecific antibodies (bsAbs) with chimeric antigen receptor T (CART) cells for PC treatment.
- To discuss the clinical development and future potential of bsAbs in PC.
Summary:
- Bispecific antibodies (bsAbs) are emerging as a promising immunotherapy for prostate cancer (PC).
- Unlike CART cells, bsAbs offer readily available 'off-the-shelf' reagents.
- bsAbs targeting STEAP1 and PSMA are under clinical evaluation for metastatic and relapsed PC, showing promising results.
Impact:
- Bispecific antibodies represent a novel therapeutic strategy for advanced prostate cancer.
- The development of bsAbs could expand treatment options for patients resistant to standard therapies.
- Further clinical evaluation of bsAbs like those targeting STEAP1 and PSMA is crucial for PC management.
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