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Published on: September 3, 2013
Targeting epitopes in prostate-specific membrane antigen for antibody therapy of prostate cancer
Y Kinoshita1, K Kuratsukuri, N Newman
1Department of Urology, SUNY Upstate Medical University, Syracuse, New York 13210, USA.
Abstract:
Prostate-specific membrane antigen (PSMA) is a target for immunotherapy of prostate cancer. It has been shown that antibodies against PSMA inhibited the in vivo growth of LNCaP tumor. In the present study, monoclonal antibodies against four epitopes in PSMA were raised. MAb 24.4E6 (IgG1), specific for the epitope (residues 638-657) in PSMA, significantly reduced the growth rate of established LNCaP tumor in SCID mice. Mouse IgG was detected in the tumor of mice treated with 24.4E6, but not with an unrelated MAb. These results suggest that this epitope may be the main target in PSMA for antibody therapy of prostate cancer.
Insights
Monoclonal antibodies targeting prostate-specific membrane antigen (PSMA) show promise for prostate cancer immunotherapy. A specific antibody, MAb 24.4E6, significantly inhibited LNCaP tumor growth in mice, indicating a key epitope for effective antibody therapy.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Prostate-specific membrane antigen (PSMA) is a validated target for prostate cancer immunotherapy.
- Previous studies demonstrated that anti-PSMA antibodies can inhibit tumor growth in vivo.
- Identifying specific, effective epitopes on PSMA is crucial for optimizing antibody-based therapies.
Purpose of the Study:
- To develop and characterize monoclonal antibodies targeting distinct epitopes of PSMA.
- To evaluate the efficacy of a novel anti-PSMA antibody, MAb 24.4E6, in inhibiting established prostate cancer tumor growth.
- To investigate the therapeutic potential of targeting a specific PSMA epitope for prostate cancer treatment.
Main Methods:
- Generation of monoclonal antibodies against four unique epitopes of PSMA.
- In vivo efficacy study using LNCaP prostate cancer xenografts in SCID mice treated with MAb 24.4E6.
- Detection of mouse IgG within tumors to confirm antibody localization and engagement.
Main Results:
- Monoclonal antibody 24.4E6, targeting an epitope within residues 638-657 of PSMA, significantly reduced the growth rate of established LNCaP tumors.
- Treatment with MAb 24.4E6 resulted in detectable mouse IgG within the tumor tissue.
- Control treatment with an unrelated monoclonal antibody did not lead to detectable IgG in the tumor.
Conclusions:
- The epitope located at residues 638-657 of PSMA is a critical target for antibody-mediated inhibition of prostate cancer growth.
- MAb 24.4E6 demonstrates significant therapeutic potential for established prostate cancer.
- These findings support the development of PSMA-targeted antibody therapies for prostate cancer, focusing on this identified epitope.

