VACCINES: GM-CSF as a Melanoma Vaccine Target

Applied Genetics News,  March, 2001  

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The Immune Response Corp. (5935 Darwin Court, Carlsbad, CA 92008; Tel: 760/431-7080, Fax: 760/431-8636, Website: imnr.com) has revealed that its novel membrane bound granulocyte macrophage- colony stimulating factor (mbGM-CSF) vaccine appears to protect against the development of melanoma (skin cancer) and colorectal cancers. They also suggest that the vaccine inhibits metastases of pre-existing tumors in mouse models.

These studies were presented by company scientists at the Keystone Symposium on Cancer Intervention in Durango, Colorado, on March 2, 2001. "We have engineered a novel gene for GM-CSF into mouse tumor cells such that they express a membrane form of this cytokine as an integral cell surface component," says Soonpin Yei, senior scientific investigator at the Immune Response Corp. "These patented mbGM-CSF tumor vaccines appear to provide effective anti- cancer benefits when given both as a preventive measure and as a treatment for already established tumors."

The company believes that the close physical proximity of the membrane bound cytokine to the tumor antigens in the mbGM-CSF vaccine may represent a highly efficient way to activate APCs and a subsequent immune response. The company believes the preclinical data generated to date supports this premise, and justifies clinical trials to evaluate these vaccines.

Groups of healthy mice were first vaccinated with either inactivated melanoma cells, the mbGM-CSF vaccine, or a buffer control. The mbGM-CSF vaccine consisted of inactivated melanoma cells that were engineered to express the additional component mbGM-CSF. Five days after the two-week period of immunization, all three groups of mice were "challenged" with B16.F10 cells, a virulent strain of melanoma.

Within 43 days of the melanoma cell challenge, all 10 animals in the buffer control group were dead, as were 7 of 10 animals from the group receiving the inactivated melanoma cells without mbGM- CSF. In contrast, 6 of 10 mbGM-CSF vaccinated animals remained alive, and three of these animals showed no evidence of tumor. These tumor-free survivors were re-challenged with live B16 tumor cells, and retained the ability to resist tumor growth for at least an additional five months.

To test for potential therapeutic benefits of the mbGM-CSF vaccine, mice with pre-existing B16.F10 tumors were established by inoculating with active melanoma cancer cells. The mice were then divided into 2 groups (10 animals per group) and treated with weekly intradermal injections of either inactivated melanoma cells or the mbGM-CSF vaccine.

All of the animals that received the vaccine without mbGM-CSF were dead within 27 days. In contrast, 100% of the mbGM-CSF vaccinated animals were still alive. Additionally, the animals that died had large tumors and intensive lung metastases, while the mbGM-CSF vaccinated mice had significantly smaller tumors than the control group and presented no evidence of lung metastases, even when evaluated histologically.

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