new trial at Ohio State of herceptin/paclitaxel/IL12 to activateNK(natrlkiller)TCELLS

Dual Stimulation Boosts Anti-Tumor Responses of Natural Killer Cell
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By Will Boggs, MD

NEW YORK (Reuters Health) Jan 24 - Natural killer cells dually stimulated by exposure to antibody-coated tumor cells plus interleukin 12 produce T cell-recruiting chemokines, according to a report in the January 1, 2006 issue of Cancer Research.

"It might be useful to give cytokines like IL-12 in combination with therapeutic antibodies in the setting of cancer," Dr. William E. Carson III from The Ohio State University, Columbus, Ohio told Reuters Health.

Dr. Carson and colleagues first examined the ability of natural killer (NK) cells to produce T cell-recruiting chemokines following dual stimulation with interleukin 2 or IL-12 and human breast cancer cells coated with the anti-HER2 antibody trastuzumab.

These in vitro studies showed that, with either IL-2 or IL-12, NK cells were potently stimulated to produce several chemokines. Supernatants from these cultures induced chemotaxis of naive and activated T cells, the results indicate.

Also, coadministration of IL-12 and trastuzumab-coated tumor cells in mice led to elevated chemokine levels, the researchers report.

Now, in a phase I trial, breast cancer patients who showed a complete clinical response or prolonged stabilization of disease after treatment with trastuzumab plus IL-12 had increased levels of chemokines throughout the course of treatment, the report indicates.

Sera from these patients induced chemotaxis of T cells, the investigators observe, and lymphocytes infiltrating the tumors of patients who exhibited a complete response to trastuzumab plus IL-12 consisted mainly of cytotoxic CD8+ T cells.

"This is preliminary data and needs to be confirmed," Dr. Carson cautioned. "Also, there are other cytokines that might be effective in addition to IL-12, such as IL-21."

He added: "These results might be important in other cancers if there is an antibody that is being used to target a protein on the surface of the cancer cell." His team is evaluating the same chemokines "in a follow-up trial in which IL-12 was given in combination with Herceptin and paclitaxel," Dr. Carson said.

Cancer Res 2006;66:517-526.