Immunotherapy

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Cytokines

Oncologists often describe cytokines, such as the various interferon and interleukin molecules, as growth factors for the immune system. Naturally occurring, there are currently about three dozen families of interleukins, labeled IL-1 through IL-36. Some interleukins are potent chemical signals that stimulate T-cell growth and activity. These include IL-2, IL-7, IL-15 and IL-21.

In 1992, high-dose interleukin-2 (IL-2) was the first immunotherapy approved by the FDA to be used as a primary or stand-alone cancer treatment. The original indication of this therapy was advanced kidney cancer. Today, high-dose IL-2 may also be used for metastatic melanoma. High-dose IL-2 treatment can result in complete remission in a small percent of kidney cancer and melanoma patients.

However, high-dose IL-2 is an intensive treatment often associated with severe toxicities that is administered in the hospital. The administration of high-dose IL-2 is limited to select cancer centers nationwide due to the complications that can be associated with its use. Seattle Cancer Care Alliance (SCCA) is the only Seattle-Tacoma area cancer center offering high-dose IL-2 to cancer patients. Our physicians specializing in melanoma and kidney cancer care have expertise in identifying appropriate patients for high dose IL-2 and guiding them through a course of this therapy.

In the Phase I clinical trials program at SCCA, studies are under way examining the anti-tumor effects of alternate T-cell growth factors including IL-15 and IL-21 that may have less toxicity than IL-2 and can be administered in an outpatient setting.

Shailender Bhatia, MD, an SCCA medical oncologist, is studying a novel approach to administering Interleukin-12 for treating melanoma and Merkel cell cancers. Dr. Bhatia’s trial actually introduces the gene for IL-12 directly into a melanoma or Merkel cell tumor. Then an electrode is inserted in the tumor to deliver a current, which tears holes in the cell membrane and allows the plasmid DNA encoding IL-12 to penetrate tumor cells. This technique is called electroporation. The gene then operates within the tumor to increase the production of IL-12. This cytokine attracts T-cells to the tumor and, ideally, they will recognize, attack, and destroy the cancer—without toxic side effects.

Plasmids are DNA molecules that carry genes and can transmit them—without actually becoming integrated into the human chromosomes. Says Dr. Bhatia, “The gene just sits there and the cell’s machinery uses the DNA to manufacture the desired protein. It’s much simpler than other kinds of gene therapy. This use of plasmids could be adapted to express any protein locally in tumors.”

IFN-alfa is another cytokine therapy that has FDA approval for use in a variety of cancers including several types of leukemia and lymphoma, kidney cancer, and melanoma. Currently, IFN-alfa is most commonly used as adjuvant therapy for high risk melanoma and for advanced kidney cancer in combination with bevacizumab. IFN-alfa can directly slow the growth of cancer cells as well as stimulate the immune system.

What to Expect

High-dose IL-2 is an intensive treatment. Recommending high dose IL-2 for patients requires careful consideration of the diagnosis, treatment history, disease status, and other medical problems the patient may have. A “course” of high-dose IL-2 consists of a one-week “cycle” in the hospital receiving the drug intravenously, followed by a week off to recover, and then a second one-week cycle. Side effects require close monitoring in an ICU-level ward.

In contrast to high-dose IL-2, IFN-alfa is a treatment delivered in an outpatient setting. Additional investigational cytokine treatments available at the center are also scheduled for outpatient administration. Anticipated side effects are far less extreme than for high-dose IL-2.