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Bispecific Antibodies in Prostate Cancer Therapy: Current Status and Perspectives
Jonas S Heitmann1,2, Martin Pfluegler1,2,3, Gundram Jung2,3,4
1Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, 72076 Tübingen, Germany.
Abstract:
Prostate carcinoma (PC) is the second most common cancer in men. When the disease becomes unresponsive to androgen deprivation therapy, the remaining treatment options are of limited benefit. Despite intense efforts, none of the T cell-based immunotherapeutic strategies that meanwhile have become a cornerstone for treatment of other malignancies is established in PC. This refers to immune checkpoint inhibition (CI), which generally reinforces T cell immunity as well as chimeric antigen receptor T (CAR-T) cells and bispecific antibodies (bsAbs) that stimulate the T cell receptor/CD3-complex and mobilize T cells in a targeted manner. In general, compared to CAR-T cells, bsAb would have the advantage of being an "off the shelf" reagent associated with less preparative effort, but at present, despite enormous efforts, neither CAR-T cells nor bsAbs are successful in solid tumors. Here, we focus on the various bispecific constructs that are presently in development for treatment of PC, and discuss underlying concepts and the state of clinical evaluation as well as future perspectives.
Insights
Prostate cancer (PC) lacks effective T cell immunotherapies like immune checkpoint inhibition, CAR-T cells, and bispecific antibodies (bsAbs). This review explores current bispecific antibody developments for PC treatment.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Prostate carcinoma (PC) is a leading cancer in men, with limited options after androgen deprivation therapy failure.
- Current T cell-based immunotherapies, successful in other cancers, are not yet established for PC.
- Existing strategies include immune checkpoint inhibition (CI), chimeric antigen receptor T (CAR-T) cells, and bispecific antibodies (bsAbs).
Purpose of the Study:
- To review bispecific antibody constructs currently in development for prostate carcinoma treatment.
- To discuss the underlying scientific concepts and clinical evaluation status of these bsAbs.
- To explore future perspectives for bsAb therapy in PC.
Main Methods:
- Review of current literature on bispecific antibody development for prostate cancer.
- Analysis of clinical trial data for bsAbs targeting PC.
- Discussion of the advantages and challenges of bsAbs compared to other immunotherapies like CAR-T cells.
Main Results:
- Bispecific antibodies (bsAbs) offer potential advantages over CAR-T cells as "off the shelf" reagents for PC.
- Despite significant efforts, neither CAR-T cells nor bsAbs have yet achieved success in solid tumors, including PC.
- Various bsAb constructs are under active development for PC treatment.
Conclusions:
- Bispecific antibodies represent a promising area of investigation for advanced prostate cancer.
- Further research and clinical evaluation are crucial to overcome challenges and establish bsAbs as an effective therapy for PC.
- Targeted T cell engagement via bsAbs holds potential for improving outcomes in PC patients unresponsive to standard therapies.
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