Interleukins Boost Effectiveness of Herceptin

Cancer researchers have found that the chemotherapeutic drug trastuzumab (Herceptin) is more effective when administered together with immune system stimulators such as interleukin-2 (IL-2) or interleukin-12 (IL-12).

Trastuzumab is a monoclonal antibody specific for HER2 protein, which is overexpressed on the membranes of many breast tumor cells. Treatment with the drug causes the cancer cells to become covered with the antibody. In the current study, investigators at Ohio State University (Columbus, USA) described the results of dual stimulation of NK (natural killer) cells with IL-2 or IL-12 and human breast cancer cells coated with trastuzumab.

They reported in the January 1, 2006, issue of Cancer Research that NK cells stimulated in this manner secreted an array of T cell-recruiting chemotactic factors, including IL-8, macrophage-derived chemokine, macrophage inflammatory protein 1-alpha (MIP-1 alpha), monocyte chemo-attractant protein 1, and regulated on activation, normal T cells expressed and secreted (RANTES), whereas stimulation of NK cells with either the interleukins alone or with only the antibody-coated tumor cells had little effect.

Injection of IL-12 and trastuzumab-coated mouse-tumor cells into mice raised the blood levels of immune-stimulating substances produced by NK cells. Furthermore, plasma samples from 15 patients with different types of cancer who were participating in a phase-I clinical trial of trastuzumab plus IL-12 showed short-term increases in the same immune-stimulating substances. Three patients who responded to the therapy demonstrated long-term increases in the NK cell products.

"This is a preliminary study and the findings must be verified,” said senior author Dr. William E. Carson III, associate professor of surgery at Ohio State University, "but overall, the evidence supports the use of immune-stimulating agents in patients who receive antibody-based drugs such as trastuzumab. Our results show that the immune system really can play an important role in this therapy and that the outcome of patients treated with antibody-based drugs might be improved by activating the patient's immune system with agents such as IL-12.”