Universal Immunity

Our immune system has ample weapons for fighting cancer, but of course nobody can win all the battles all the time. As we know only too well, it is often the tumor that gains the upper hand, outsmarting the body’s anti-cancer defenses. One of the latest attempts to boost these defenses is the so-called adoptive cell transfer, in which patients receive a therapeutic injection of their own immune cells. This therapy, currently being tested in early clinical trials of melanoma and neuroblastoma, has its limitations: Removing immune cells from a patient, not to mention growing these cells outside the body for future reinjection, is extremely expensive and not always technically feasible.

 

Weizmann Institute scientists have now tested in mice a new form of adoptive cell transfer that overcomes these limitations while enhancing the tumor-fighting ability of the transferred cells. The research, reported recently in Blood, was performed in the lab of Prof. Zelig Eshhar of the Institute’s Immunology Department by graduate student Assaf Marcus and lab technician Tova Waks.

The new approach should be more readily applicable than the existing adoptive cell transfer treatments because it relies on a donor pool of immune T cells, prepared in advance, rather than on the patient’s own cells. Moreover, using a method pioneered by Prof. Eshhar more than two decades ago, these T cells are outfitted with receptors that specifically seek out and identify the tumor, thereby promoting its destruction.

In the study, the scientists first suppressed the immune system of mice by a relatively mild dose of radiation; they then administered a controlled dose of the modified donor T cells. The mild suppression temporarily prevented the donor T cells from being rejected by the recipient, but it didn’t prevent the cells themselves from attacking the recipient’s body, particularly the tumor. This attack was precisely what rendered the therapy so effective: while the rejection of the donor T cells was being delayed, these cells had sufficient opportunity to destroy the tumor.

If this method works in humans as well as it did in mice, it could lead to an affordable cell transfer therapy for a wide variety of cancers. Such therapy would rely on an off-the-shelf pool of donor T cells equipped with receptors for zeroing in on different types of cancerous cells.

Proof of Concept

In August 2011, University of Pennsylvania researchers reported in The New England Journal of Medicine that they had successfully used Prof. Zelig Eshhar’s original, adoptive cell transfer approach in a pilot trial of patients with chronic lymphocytic leukemia. The patients were treated with T bodies – genetically engineered versions of their own T cells. “This study has provided a proof of concept for the potency of our T-body therapy: previously shown to work in mice, it has now proved beneficial in cancer patients,” Prof. Eshhar said. “Within three weeks, the tumors had been blown away, in a way that was much more violent than we ever expected,” said senior author Carl June, MD, professor of Pathology and Laboratory Medicine in the University of Pennsylvania’s Abramson Cancer Center, who led the trial. “It worked much better than we thought it would. ”

Encouraged by this initial success, Dr. June and colleagues plan to apply the method to the treatment of other malignancies, including non-Hodgkin lymphoma, acute lymphocytic leukemia and childhood leukemia that is not alleviated by standard family. They also consider using the T bodies in patients with solid tumors, such as ovarian and pancreatic cancer.

 

Prof. Zelig Eshhar’s research is supported by the M.D. Moross Institute for Cancer Research; the Leona M. and Harry B. Helmsley Charitable Trust; the Kirk Center for Childhood Cancer and Immunological Disorders; and the estate of Raymond Lapon.