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PR1--a monoclonal antibody that reacts with an antigen on the surface of normal and malignant prostate cells
I Pastan1, E Lovelace, A V Rutherford
1Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Md 20892.
Background:
The principal treatment for prostate cancer is surgery; prostate cancer is resistant to the common anticancer drugs. The only useful therapy for metastases involves diminishing testosterone levels by orchiectomy or administration of drugs, either of which may increase survival time. One approach to prostate cancer treatment is to use a monoclonal antibody (MAb) to target cytotoxic substances to these cancer cells. The MAbs available either do not react uniformly with prostate cancer cells or react with normal tissues. Thus, a new MAb is needed.
Purpose:
The goal of this study was to isolate an MAb that reacts with an antigen present on the surface of prostate cancer cells.
Methods:
A strain of prostate cancer cells was isolated from a prostate cancer specimen, grown for 2-4 weeks in short-term culture, and used to immunize BALB/c mice. Hybridomas were then prepared by using spleen cells from the immunized mice. One hybridoma produced an MAb (PR1) that reacted with prostate cancers.
Results:
MAb PR1 is an IgMK subtype that reacts uniformly with the surface of most (25 of 26) adenocarcinomas of the prostate. It also reacts with the surface antigen on normal prostate epithelial cells and on cells from benign prostatic hyperplasia. MAb PR1 reacts with a limited number of normal tissues including a subset of principal cells located in the collecting ducts of the kidney.
Conclusion:
We conclude that MAb PR1 reacts with a differentiation antigen present in normal prostate and that this antigen continues to be expressed on almost all adenocarcinomas of the prostate.
Implications:
This antibody may be useful for the diagnosis of or therapy for prostate cancer.
Insights
Researchers developed a new monoclonal antibody (MAb) called PR1. This MAb targets a prostate cancer antigen, offering potential for improved diagnosis and therapy for prostate cancer.
Area of Science:
- Immunology and Oncology
- Development of targeted cancer therapies
Background:
- Prostate cancer treatment relies primarily on surgery, with limited efficacy of conventional chemotherapy.
- Current therapies for metastatic prostate cancer focus on androgen deprivation, which has survival benefits.
- Existing monoclonal antibodies (MAbs) for prostate cancer lack specificity or react with normal tissues, necessitating new MAb development.
Purpose of the Study:
- To isolate a novel monoclonal antibody (MAb) that specifically targets an antigen on the surface of prostate cancer cells.
Main Methods:
- Prostate cancer cells were isolated from patient specimens and cultured.
- BALB/c mice were immunized with these cultured cells.
- Hybridomas were generated from spleen cells of immunized mice to produce MAbs.
Main Results:
- A specific MAb, designated PR1 (IgMK subtype), was identified.
- PR1 uniformly reacts with the surface antigen of 25 out of 26 prostate adenocarcinomas.
- PR1 also binds to antigens on normal prostate epithelial cells, benign prostatic hyperplasia cells, and a subset of kidney collecting duct cells.
Conclusions:
- MAb PR1 recognizes a differentiation antigen expressed on normal prostate tissue and consistently on most prostate adenocarcinomas.
- The PR1 antibody shows potential utility in the diagnosis and therapeutic strategies for prostate cancer.
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