In recent years, thanks to a string of high-profile success stories, immune therapy has emerged as one of the most promising approaches to fighting cancer (See “Cancer’s Super-Survivors” in the Wall Street Journal). Building on that recent success, a wave of powerful new therapies are now being developed, including therapeutic vaccines, oncolytic viruses such as a polio-based treatment recently featured on 60 Minutes, and drugs called immune checkpoint inhibitors that block the ability of tumor cells to hide from the immune system.
To help chordoma patients take advantage of this promising new class of therapies, we have recently worked with Dr. Michael Lim at Johns Hopkins University and collaborators at the Jackson Laboratory to develop the first chordoma mouse model suitable for testing immune therapies. Most mouse models of cancer, including the patient-derived xenograft models of chordoma developed in recent years, involve human tumors implanted into mice that lack a functioning immune system, and, thus, do not reject foreign cells (mice with functional immune systems reject tumors just like people reject organs from other individuals). However, these xenograft mouse models cannot be used to test immune therapies, which work by stimulating the immune system to attack cancer cells.
To overcome this limitation, with guidance from Dr. Lim, last year we contracted with the Jackson Laboratory to develop mice with a functional human immune system, known as “humanized” mice. The immune system of these mice is engineered to match the immune fingerprint of the precise patient whose tumor they will harbor. After nearly a year developing these mice, the first mice were delivered to Dr. Lim in January and are now being studied in his lab.
In February, with an initial $30,000 seed grant, we began funding Dr. Lim to test promising therapies in this new model, starting with a class of drugs called checkpoint inhibitors. This project builds upon findings from Lim’s previous Foundation-funded study in which he successfully demonstrated that chordomas express immune checkpoint molecules that may enable the tumors to evade destruction by the immune system. His findings were published in the January 2015 issue of the Journal of Neuro-oncology (see article here).
By testing checkpoint inhibitors in the new humanized mouse models, Dr. Lim aims to determine which checkpoint inhibitors or combinations thereof are most likely to be effective in chordoma. Preliminary results from this study are anticipated by year’s end. If positive, the goal would be to initiate a human clinical trial with one or more checkpoint inhibitors that are being developed. Meanwhile, we continue to work with Dr. Lim and other researchers to explore the potential of a variety of types of immune therapy for the treatment of chordoma.