J591 May Be Effective Against Vascular Cells of Prostate, Renal, Bladder, and Colon Cancers
New York, NY (May 19, 2002) — A physician in Weill Cornell Medical College's Division of Hematology/Oncology is reporting that a recently developed monoclonal antibody, called J591, targets an antigen expressed in the blood vessels of solid tumors. The physician, Dr. Matthew I. Milowsky, who is just finishing a term as a fellow in the division, makes his presentation today to the American Society of Clinical Oncologists (ASCO), which is meeting in Orlando, FL.
Dr. Milowsky, who will become an Assistant Professor in the division this July, explains that J591 was developed by a colleague, Dr. Neil Bander, and manufactured by Millennium Pharmaceuticals, of Cambridge, MA. "J591 recognizes the extracellular domain of prostate-specific membrane antigen (PSMA)," Dr. Milowsky says. PSMA, so named because it was first found in the prostate, is present in the blood vessels of numerous solid tumors, but not in normal blood vessels of benign tissues. The hope is that by attaching a radioactive molecule or other anti-cancer agent to J591, doctors will be able to target tumors specifically for the delivery of therapy.
Dr. Milowsky presents, today, the results of a Phase I trial of J591, testing its safety, dosing, and accuracy in targeting PSMA. The trial involved J591 that had been "labeled" with an isotope of indium so that the investigators could track where the monoclonal antibody traveled. Nine cancer patients received either 5 milligrams or 10 milligrams of J591, followed by a second dose 14 days later. There were, at first, reactions to the infusion, including one case of bronchospasm in a patient with lung cancer, but these were prevented with acetominophen and diphenhydramine. Radioisotope scans of the patients showed that the monoclonal antibody successfully and specifically targeted the tumor sites of 6 of the 9 patients.
Dr. Milowsky concludes, "J591 specifically targets vascular endothelial cells of solid tumors, including renal, bladder, and colon cancer. Monoclonal antibody J591 may be an effective approach to target vascular endothelial cells of solid tumors with radioactivity or other cytotoxins."
Besides Dr. Bander, the Bernard and Josephine Chaus Professor of Urological Oncology at Weill Cornell, the other investigators are A.S. Rosmarin, M.V. Cobham, M.R. Navarro, R.S. Keresztes, L. Kostakoglu, P. Smith-Jones, S. Vallabhajosula, S.W. Kim, H. Liu, S.J. Goldsmith, and D.M. Nanus. The study was supported by CaPCURE and BZL Biologics.
Other J591 Study Findings: Prostate Cancer Studies
In another presentation today at ASCO, Dr. Bander presents interim results on two studies measuring the effects of two distinct radioisotopes attached to J591, 177Lu (Lutetium) and 90Y (Yttrium), in advanced prostate cancer. The studies included 48 patients whose prostate cancer had spread throughout the body and whose disease was progressing despite having received both hormonal treatment and, in most of the cases, chemotherapy.
In these trials, which were also Phase I trials, the dose is progressively increased in groups of patients in order to determine the maximal tolerated dose. Thus far, therapy with the radiolabeled antibodies is well tolerated, and patients have developed no symptoms as a result of the treatment. Blood tests reveal a drop in platelet counts — Âwhich was anticipated —Â and then a spontaneous return to normal. The low frequency of side effects may be due, in part, to the fact that J591 was "deimmunized," or altered to minimize the chances that the body's immune system would develop an allergic response to it. In addition, J591's targeting only of tumor and not normal cells may have minimized side effects.
Although these are Phase I trials, designed primarily to define doses and toxicity rather than anti-tumor response, patients treated with each radiolabeled version of J591 have experienced dose-related anti-tumor activity. Interim results to date have shown that J591 attached either to 90Y or 177Lu helped reduce PSA levels in patients by as much as 85%. The maximum tolerated dose is yet to be determined.
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