Related Experiment Video
Updated: Dec 21, 2025
Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
A novel bispecific antibody targeting CD3 and prolactin receptor (PRLR) against PRLR-expression breast cancer
Yuexian Zhou1,2, Huifang Zong1,2, Lei Han1,2
1Engineering Research Center of Cell & Therapeutic Antibody, MOE,Shanghai Jiao Tong University, Dongchuan Road, Shanghai, China.
Background:
Prolactin receptor (PRLR) is highly expressed in a subset of human breast cancer and prostate cancer, which makes it a potential target for cancer treatment. In clinical trials, the blockade of PRLR was shown to be safe but with poor efficacy. It is therefore urgent to develop new therapies against PRLR target. Bispecific antibodies (BsAbs) could guide immune cells toward tumor cells, and produced remarkable effects in some cancers.
Methods:
In this study, a bispecific antibody targeting both tumor antigen PRLR and T cell surface CD3 antigen (PRLR-DbsAb) was constructed by split intein mediated protein transsplicing (BAPTS) system for the first time. Its binding activity was determined by Biacore and Flow cytometry, and target-dependent T cell mediated cytotoxicity was detected using LDH release assay. ELISA was utilized to study the secretion of cytokines by immune cells. Subcutaneous tumor mouse models were used to analyze the in vivo anti-tumor effects of PRLR-DbsAb.
Results:
PRLR-DbsAb in vitro could recruit and activate T cells to promote the release of Th1 cytokines IFN- γ and TNF- α, which could kill PRLR expressed breast cancer cells. In xenograft models with breast cancer cell line T47D, NOD/SCID mice intraperitoneally injected with PRLR-DbsAb exhibited significant inhibition of tumor growth and a longer survival compared to mice treated with PRLR monoclonal antibody (PRLR mAb).
Conclusions:
Both in vitro and in vivo experiments showed PRLR-DbsAb had a potential therapy of cancer treatment potential therapy for cancer. Immunotherapy may be a promising treatment against the tumor target of PRLR.
Insights
A novel bispecific antibody targeting prolactin receptor (PRLR) and CD3 effectively recruits T cells to kill PRLR-expressing breast cancer cells. This immunotherapy approach shows significant anti-tumor effects in vivo, offering a promising new cancer treatment strategy.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Prolactin receptor (PRLR) is a potential therapeutic target in breast and prostate cancers.
- Previous PRLR blockade showed safety but limited efficacy, necessitating novel treatment strategies.
- Bispecific antibodies (BsAbs) can redirect immune cells to target cancer cells.
Purpose of the Study:
- To construct and evaluate a novel bispecific antibody targeting both PRLR and CD3 (PRLR-DbsAb).
- To assess the in vitro and in vivo anti-tumor efficacy of PRLR-DbsAb.
Main Methods:
- PRLR-DbsAb was engineered using a split intein mediated protein transsplicing (BAPTS) system.
- Binding activity, T cell-mediated cytotoxicity (LDH assay), and cytokine secretion (ELISA) were analyzed.
- In vivo anti-tumor effects were evaluated in subcutaneous tumor mouse models.
Main Results:
- PRLR-DbsAb successfully recruited and activated T cells, leading to IFN-γ and TNF-α release.
- The antibody demonstrated potent killing of PRLR-expressing breast cancer cells in vitro.
- In vivo studies showed significant tumor growth inhibition and improved survival in mice treated with PRLR-DbsAb compared to PRLR mAb.
Conclusions:
- PRLR-DbsAb exhibits significant potential as a cancer therapeutic agent.
- This bispecific antibody represents a promising immunotherapy strategy for targeting PRLR-expressing cancers.
