Researchers at UCLA's Jonsson Cancer Center have shown for the first time that immunotherapy delivered via gene therapy may prove to be a potent weapon in the fight against locally advanced prostate cancer, according to an article published Sunday (May 20) in the peer-reviewed journal Human Gene Therapy.
Lead author Dr. Arie Belldegrun, chief of urologic oncology at the Jonsson Cancer Center, said his early phase study suggests that intra-tumoral immunotherapy, in combination with surgery to remove the prostate, represents a new option for treating men with cancer that has spread beyond the boundaries of the prostate.
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."
The study outlined in the article involves injecting 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 to be 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. And in more than half of the patients, the therapy resulted in reduced PSA levels, a blood marker that signals the presence of prostate cancer.
"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.
A hormone-like substance, IL-2 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 is active against prostate cancer.
Belldegrun and his team of researchers use gene therapy to deliver the IL-2 to the prostate, a novel approach in 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 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, 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's most common in 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. - By Kambra McConnel
UCLA's Jonsson Cancer Center
[Contact: Kambra McConnel]