Prof. Lea Eisenbach is a pioneer in the field of cryoimmunotherapy. As its name suggests, this approach combines two forms of treatment: cryosurgery, from the Greek cryo, for “icy cold,” and immunotherapy, which harnesses the tools of the immune system. The combination of these two accepted treatments of cancer results in an innovative approach that has produced promising results in the lab.
Eisenbach, of the Weizmann Institute’s Immunology Department, began to experiment with this method some ten years ago, when a physician interning in her lab suggested they look into a technique known as cryosurgery, which is not really surgery at all. Rather, a tumor is pierced a number of times with a needle previously frozen in liquid nitrogen, and the repeated freezing and thawing causes tumor cells to burst and die. This treatment, used increasingly in the past few decades to eliminate cancerous tumors of the prostate, liver, kidney and other organs, causes less damage to surrounding tissue than regular surgery. Yet another advantage: The destruction of tumor cells triggers inflammation, which activates the immune system, prompting it to fight the cancer. This activation, however, does not necessarily prevent the cancer from spreading to other organs. So the goal of cryoimmunotherapy is to enhance the effectiveness of the immune response in metastasis, when the cancer in on the move.
Several years ago, Eisenbach’s team performed cryosurgery on mice that had cancer metastases in the lungs, after which they injected these mice with dendritic cells – cells that detect infectious organisms, malignancy and other dangers, and activate the immune system accordingly. The mice that received the cellular injections remained disease-free for longer periods and lived longer than those treated with cryosurgery alone. But ultimately, only half of them survived.
In the healthy lymph node, dendritic cells (green) form interconnected networks in which T cells (red) migrate. Image: lab of Dr. Guy Shakhar
In a recent study,
research student Zoya Alteber and other members of Eisenbach’s team have managed to improve this survival rate. As reported in Cancer Immunology and Immunotherapy,
they treated mice that had lung metastases in the same manner as before, with cryosurgery and injections of dendritic cells, but added an injection of molecules called CpG-ODNs, known to provoke a strong immune response. These molecules, present on the surfaces of bacteria and viruses, bind to receptors on dendritic cells, causing these cells to unleash a chain of biochemical signals that results in the release of various immune chemicals and in the activation of immune T killer cells, which fight malignancy.
Indeed, the scientists found that about a week after the treatment, the mice had increased levels of several immune chemicals called cytokines, as well as high levels of T killer cells, in their lymph nodes and elsewhere. But most important, mice that received the dual immune treatment had almost no lung metastases, and about three-quarters of them survived – a marked improvement over the results of the earlier study.
Moreover, when the scientists later injected the surviving mice with malignant cells, these cells were eliminated by the immune system, so they produced no tumors. T killer cells and other components of the immune system had evidently retained a memory of their previous antitumor response, protecting the mice against a cancer relapse.
Taking part in the study were Drs. Meir Azulay, Gal Cafri and Esther Tzehoval, as well as Ezra Vadai, all of Eisenbach’s lab.
Yeda Research & Development Co., the Weizmann Institute’s technology transfer arm, has filed a patent for the dual immune therapy to accompany cryosurgery. If developed further for use in humans, it may be employed in the future to treat various types of cancer while at the same time preventing metastases.
Prof. Lea Eisenbach’s research is supported by the Jeanne and Joseph Nissim Foundation for Life Sciences Research; the Victor Pastor Fund for Cellular Disease Research; the Pearl Welinsky Merlo Foundation Scientific Progress Research Fund; the Lewis Family Charitable Trust; and the estate of John Hunter. Prof. Eisenbach is the incumbent of the Georg F. Duckwitz Professorial Chair of Cancer Research.