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New Method of Teaching Immune System to Recognize A Prostate Cancer Marker, PSMA

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PSMA (prostate specific membrane antigen) is a marker expressed in advanced prostate cancer in many men including men with bone metastases. Several methods of exploiting it to target cells and prostate  tumors are in clinical trials or under research. Prostate cancer patients in an ongoing Phase 1 study have been treated with designer T cells modified by retroviral gene therapy.

The patients’ own T cells  are taught to attack tumors in the body by targeting PSMA. The method has been developed by researchers  at Boston University School of Medicine and the Roger Williams Medical Center in Providence, R.I.. They believe their method may help cancer therapy enter into a new era of what they call living drugs.

The concept is similar to that used in the production of Provenge, which is in Phase 3 trials. Provenge aims to teach the individual patient's T-cells to recognize and target PAP (prostate acid phosphatase). This new therapy uses a retrovirus andtrains T-cells to recognize and target PSMA (prostate specific membrane antigen). In most men with prostate cancer, both PAP and PSMA are over-expressed by prostate cancer cells and elevated in circulating blood.

Richard Junghans, MD PhDRichard Junghans, M.D., Ph.D., associate professor of surgery and medicine, who is in charge of the Phase 1 Trial of Anti-PSMA Designer T Cells in Advanced Prostate Cacer  ongoing at Rhode Islands' Roger Williams Medical Center, says: "This is the brave new world of oncology treatments because these 'drugs' are alive rather than inert chemicals. These designer T cells will be able to go and attack cancers where hormone therapies and chemotherapies have failed.”

In the Phase 1 trial of the newer, PSMA vaccine chemotherapy is being used to create a "hematologic space” in the body, Junghans said, a space in which the designer T cells expand 100-fold in number after infusion to increase their potency. In the first two patients treated, researchers noted prostate-specific antigen reductions of 50 percent to 75 percent.

“With still higher doses of T cells soon to follow in our dose escalation plan, we hope to observe the 100 percent prostate-specific antigen reductions that everyone seeks,” Junghans  said. “This genetic engineering brings us into a new era of cancer treatment by reprogramming T cells to attack the cancer in the same way that the T cells would normally fight a virus infection. I predict we will see approval of drugs in this category in the next five years.”

Junghans is scheduled to present data on the patients in this phase I trial at the Centennial Meeting of American Association for Cancer Research this week in Denver, CO.

The Phase I trial referenced in the above is up and running and recruiting patients in Rhode Island at Roger Williams Medical Center (Richard P. Junghans, PhD, MD; Principal Investigator). The study is called:

Trial of Anti-PSMA Designer T Cells in Advanced Prostate Cancer After Non-Myeloablative Conditioning

This clinical trial is funded under a grant from the US Army Department of Defense Prostate Cancer Research Program to Dr Richard Junghans. The trial is supported by Amgen and Novartis with contributions of ancillary drug components. The preclinical development of this agent was conducted under funding from the Prostate Cancer Foundation. 

To show the trend, under search words "prostate cancer, psma, treat" 9 studies are listed currently at clinicaltrials.gov as open or active but no longer recruiting: http://www.clinicaltrials.gov/ct2/results?term=prostate+cancer%2C+psma 

Search words "prostate cancer, vaccine therapy" currently brings up over 70 clinical trials
http://www.clinicaltrials.gov/ct2/results?term=prostate+cancer%2C+vaccine+therapy 

 LINKS

Dendreon CEO Mitchell Gold talks about Provenge

posted April 18 2009

Another method of targeting PSMA published this week in Prostate 2009 Apr 14:
Prostate-specific membrane antigen retargeted measles virotherapy for the treatment of prostate cancer
Liu C, et al. Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.

European Urology, 2002
Induction of Antibodies against Prostate-Specific Membrane Antigen (PSMA) by Vaccination with a PSMA DNA Vector

 

Compiled and edited by J. Strax.

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