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IL-2 Immunotherapy Curbs Locally Advanced Prostate Cancer

May 24, 2001, New York -- Researchers at UCLA's Jonsson Cancer Center have shown for the first time that an immune system booster delivered by gene therapy may prove to be a potent weapon in the fight against locally advanced prostate cancer, according to an article in Human Gene Therapy.

What is IL-2?

(Ask Graylab Med Dictionary)
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What does Interleukin-2 do to other cancers
(renal and melanoma)
and for AIDS?

"Unlike surgery, radiation, or chemotherapy, treatment with interleukin-2 does not attack the cancer cells directly. It relays the message to the immune system to boost and activate the production of specific T cells. These activated T cells then target and kill the cancer cells."
Chiron.com

(Systemic) Interleukin-2 therapy linked to heart syndrome (Reuters)

IL-2 for AIDS (immunet.org)

 
 

Arie Belldegrun, chief of urologic oncology at the Jonsson Cancer Center, said intra-tumoral immunotherapy plus surgery to remove the prostate may present a new option for treating men whose cancer has spread beyond the boundaries of the prostate.

Following up on promising lab work, Belledegrun's team injected gene-based immunotherapy -- using an ultrasound guidance system -- directly into the diseased prostate prior to surgery or after the failure of radiation therapy.

The treatment proved safe; and because the therapy was injected into the prostate and not delivered systemically, as chemotherapy is, it resulted in few side effects, Belldegrun said (see side panel for heart problems from systemic IL-2).

In more than half of the patients, the therapy resulted in reduced levels of PSA, a blood marker that signals the presence of prostate cancer.

Historically, prostate cancer was believed to be resistant to immunotherapy. Belldegrun said his study proves otherwise.

"Based on our earlier studies in the laboratory, which were published in the journal Cancer, we suspected that this approach might work in humans," he said. "We did not know, however, that gene therapy and immunotherapy could be options for patients with locally advanced prostate cancer, a high-risk group to whom we have little to offer right now."

"This is the first clinical study of its kind aimed at exploring the role of immunotherapy and gene therapy in prostate cancer patients," Belldegrun said. "We're encouraged by the significant reductions of PSA levels and by the clinical outcome in this high risk group of patients."

In this study, 24 patients with locally advanced prostate cancer were treated with gene-based immunotherapy. A gene that expresses interleukin 2 (IL-2) was injected directly into the prostate. IL-2, which is a hormone-like chemical messenger, stimulates the immune system to attract so-called "killer cells" called lymphocytes, which researchers hope will seek out and destroy cancer cells, Belldegrun said. The study proved for the first time that IL-2 delivered this way, by gene therapy, is active against prostate cancer.

The IL-2 is a passenger of sorts, riding in the gene therapy vehicle, Belldegrun said. The injection itself is done on an outpatient basis, so no hospital stays are necessary. The use of ultrasound for guidance allows researchers to deliver therapy with great accuracy.

"We proved this is a feasible approach for patients with locally advanced prostate cancer," said Dr. Robert Figlin, an oncologist at UCLA's Jonsson Cancer Center, co-author of the study and a professor of medicine and urology at the UCLA School of Medicine. "Because of its location, we were able to inject into the prostate these genes that stimulate the immune system to fight cancer. We anticipate that, in the near future, newer and more powerful agents will be delivered directly to the prostate via gene therapy - perhaps eliminating the need to remove the prostate. This is an important new concept and a proof of principal that the technology can work."

Because of the success in this early study, five centers nationwide, including UCLA's Jonsson Cancer Center, are now testing this treatment method in much larger phase II studies, Belldegrun said.

"We are encouraged by these early results and consider them valuable, especially in light of the apparent safety and lack of toxicity seen with this treatment," the Human Gene Therapy article states. "These results provide the foundation for the principle of locally administered gene therapeutic modalities in the treatment of prostate cancer."

If prostate cancer is discovered early enough, surgery, brachytherapy or external beam radiation is often all that's needed to eliminate the cancer. But when patients are diagnosed after the cancer has spread beyond the prostate, options are limited and survival rates decrease, Belldegrun said.

The difficulty is that early stage prostate cancer often results in few symptoms, so patients may not know they have the disease until after it has spread. In advanced prostate cancer, symptoms can include trouble having or keeping an erection, interrupted urine stream, urinary retention leadign to kidney failure, blood in the urine, swollen lymph nodes in the groin area and pain in the pelvic area.

Other than skin cancer, prostate cancer is the most common type of cancer found in American men, according to the American Cancer Society. About 198,000 new cases of prostate cancer will be diagnosed in the United States this year. About 31,500 men will die.

Although men of any age can get prostate cancer, it mostly affects males over 50. Men should be screened beginning at age 50. Those at high risk -- African Americans and men with family members diagnosed with prostate cancer at a young age -- should be screened beginning at age 45 or in some specialists' opinions, at age 40.
edited by J Strax

Links to Trials and Abstracts

1) Trial Info

Leuvectin Followed By Surgery in Treating Patients With Stage II or Stage III Prostate Cancer Phase II Study.

California Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California, 90095-1781, United States; Recruiting Robert Alan Figlin 310-825-5788

Ohio Cleveland Clinic Taussig Cancer Center, Cleveland, Ohio, 44195, United States; Recruiting Eric Klein 216-444-5591

Arie Belldegrun, Study Chair Jonsson Comprehensive Cancer Center.

Compare --

PSA-Based Vaccine and/or Radiotherapy to Treat Localized Prostate Cancer Phase II Study

PSA Vaccine or Nilutamide to Treat Advanced Prostate Cancer Phase II

Location, Maryland -- National Cancer Institute (NCI), 9000 Rockville Pike Bethesda, Maryland, 20892, United States; Recruiting PRPL 1-800-411-1222

2) Abstracts

Urology 2001 Apr;57(4 Suppl 1):95-9 New biologicals for prostate cancer prevention: Genes, vaccines, and immune-based interventions. Pantuck AJ, Zisman A, Henderson D, Wilson D, Schreiber A, Belldegrun A. UCLA School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1738 , USA.

Cancer J 2000 Jul-Aug;6(4):220-33 Comment in: Cancer J. 2000 Jul-Aug;6(4):213-4 Androgen deprivation induces selective outgrowth of aggressive hormone-refractory prostate cancer clones expressing distinct cellular and molecular properties not present in parental androgen-dependent cancer cells. Tso CL, McBride WH, Sun J, Patel B, Tsui KH, Paik SH, Gitlitz B, Caliliw R, van Ophoven A, Wu L, deKernion J, Belldegrun A. Department of Urology, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, USA.

World J Urol 2000 Apr;18(2):143-7 Gene therapy for prostate cancer at the University of California, Los Angeles: preliminary results and future directions. Pantuck AJ, Zisman A, Belldegrun AS. Department of Urology, University of California School of Medicine, Los Angeles 90095-1738, USA. "What once belonged to the realm of basic science is now entering the domain of phase II clinical trials. In this review, current results and future directions in prostate gene therapy at the University of California, Los Angeles, are discussed."

World J Urol 2000 Apr;18(2):121-4 Ad5CMVp53 gene therapy for locally advanced prostate cancer--where do we stand? Sweeney P, Pisters LL. Department of Urology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.

Anticancer Res 2000 Nov-Dec;20(6B):4495-8 Treatment of metastatic hormone-refractory prostate adenocarcinoma (MatLyLu) in Copenhagen rats with micro-osmotic interleukin-2 pumps. Hautmann S, Huland E, Wullbrand A, Friedrich M, Huland H. Department of Urology, University Hospital Hamburg-Eppendorf, Martintistr. 52, 20246 Hamburg, Germany.

Lamm DL, Riggs DR. Enhanced immunocompetence by garlic: role in bladder cancer and other malignancies. J Nutr. 2001 Mar;131(3s):1067S-70S. Review.

2000 Nov 1;5(6):265-273 Clinical trials of immunotherapy for advanced prostate cancer. Kuratsukuri K, Nishisaka N, Jones RF, Wang CY, Haas GP. Department of Urology, SUNY Upstate Medical University, and VA Medical Center, 750 E. Adams St., 13210, Syracuse, NY, USA

Semin Oncol 1999 Aug;26(4):455-71 Gene therapy for prostate cancer. Hrouda D, Perry M, Dalgleish AG. Department of Oncology, St George's Hospital Medical School, London, UK.

For more information on prostate cancer studies at UCLA's Jonsson Cancer Center, call toll-free clinical trials hotline at 888-798-0719.

For more information about UCLA's Jonsson Cancer Center, its people and resources, visit site on the World Wide Web at http://www.cancer.mednet.ucla.edu.

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