Combination melanoma vaccine, IL-2 extends disease free cancer survival
A phase III clinical trial that combines melanoma vaccine with immunotherapy, shows promise for preventing progression of deadly melanoma that claimed 8700 lives in the U.S. in 2010.
In research led by scientists from The University of Texas MD Anderson Cancer Center and Indiana University Health Goshen Center for Cancer Care, the combination of the first cancer vaccine and Interleukin -2 (IL2), an immune stimulating drug, improved outcomes for patients diagnosed with melanoma.
The trial, which started a decade ago, included 185 patients at 21 centers across the country. The melanoma vaccine, known as gp100:209-217 (200M), works by stimulating T cells that attack antigens on the surface of cancer cells.
Fighting melanoma with the immune system spares healthy tissue
Patrick Hwu, M.D., professor and Chair of the Department of Melanoma Medical Oncology and the study’s senior author explains the combination of the vaccine and interleukin-2, a cytokine that also activates the immune system, provides "a mechanism for ridding the body of cancer without destroying healthy tissue.”
The phase III trial randomized patients to receive the melanoma vaccine, interleukin-2 combination, or interleukin-2 alone. The primary endpoints included response rates. Secondary endpoints included toxic effects of the treatment and survival without progression of melanoma.
All of the patients in the melanoma vaccine trial had advanced disease that had spread to other organs.
In the IL2, melanoma vaccine arm of the trial, 86 patients were treated and 85 were evaluated for response.
Compared to patients who received the vaccine to those who did not, the response rate was 16 percent - progression-free survival was 2.2 months versus 6 percent and 1.6 months.
“This is one of the first positive randomized vaccine trials in cancer and the findings represent a significant step forward for treatment of advanced melanoma,” said Douglas Schwartzentruber, M.D., the medical director of the Goshen Center for Cancer Care who was involved in developing the vaccine.
“However, the vaccine only can be given to half of those with melanoma because it has to match a patient’s tissue type, or HLA. A major priority for us is to figure out ways to broaden our approach and use mixtures of peptides, for example, so that more patients are eligible.”
The melanoma vaccine works so well because the T cells that are stimulated secrete enzymes that poke holes in the membrane of the tumor cells, causing them to disintegrate.
Melanoma phase III clinical trial shows success.
The researchers hope to improve the fight against melanoma by adding immune stimulating agents to patient treatment options, given the success of the current trial. Suggestions include improved vaccine conjugates, antibodies and other cytokines that stimulate immune function like IL2.
Hwu says, “Now, our focus will need to turn toward studying these novel therapies in combination and continue our quest for better vaccines, as well as researching ways to make the study inclusive of more metastatic melanoma patients.”
"gp100 Peptide Vaccine and Interleukin-2 in Patients with Advanced Melanoma"
Douglas J. Schwartzentruber, M.D., David H. Lawson, M.D., et al
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