Combination Therapy Wipes Out Breast Tumors in Mice

Process makes tumors more sensitive to chemotherapy to improve targeted therapy.

A specific type of breast tumor was eradicated in mice by disabling a cancer-causing pathway and administering an immune-molecule-based mop-up therapy, during a recent study at the Perelman School of Medicine at the University of Pennsylvania.

“This line of research is important to future therapy for Her2-positive breast cancers because it defines a way to make the current treatment better and to use less amount of cancer drugs such as Herceptin by an ordered combination use with before interferon-gamma, which is also a clinically used drug,” said coauthor Hongtao Zhang, PhD, a research assistant professor of Pathology and Laboratory Medicine.

Anti-erbB2/neu monoclonal antibodies (mAbs) only work in 30% of breast cancer patients carrying the amplified target and cost about $100,000 a year.

This type of treatment requires a combination with chemotherapy to increase the proportion of patients it can help.

The study showed that treatment with Herceptin or lapatanib followed by interferon-gamma significantly improved tumor eradication in mice. The 2-step process works to make the tumors more sensitive to chemotherapy, which is needed to make the targeted therapy work.

“This in turn, reduces the cost of treatment so that individuals previously not able to afford targeted therapy will be able to do so. All of the therapeutic agents used in this preclinical study are approved and we expect to try ordered therapy plus interferon in clinical trials soon,” said Mark Greene, MD, PhD, the John W. Eckman Professor of Medical Science.

When considered for use in humans, the therapy would be beneficial in reducing toxicity because the amount of antibody could be decreased by approximately 66% and chemotherapy by at least 50%.

“We examined the biologic effects of interferon-gamma alone or after anti-erbB2/neu antibody treatment of erbB2-positive cells and mice,” said co-first author Yasuhiro Nagai, PhD, a postdoctoral fellow in the department of Pathology and Laboratory Medicine.

Interferon-gamma is renowned as a cytokine for immunologists but is not used as much by oncologists due to the fact that it has many side effects.

The treatment works by making the tumor cells more susceptible to Her-2 inhibitors so that they can be killed more effectively.

Moreover, the combination therapy works to grow host tumor immunity, which can be a good advantage for this therapy.

A series of experiments that examined breast cancer cell lines and transgenic mice that develop breast cancer as adults showed that interferon-gamma on its own had no effect on tumors.

However, treatment of the tumors with anti-erbB2/neu mAbs with subsequent interferon-gamma led to a considerable inhibition of tumor growth and reduction of tumor size in the mice when combined with chemotherapy.