A group of Israeli researchers, in cooperation with American colleagues, precisely isolated anti-tumor white blood cells in the immune systems of a small group of cancer patients, multiplied them and reintroduced this enhanced army of personalized disease-fighting cells to the patients, obtaining surprisingly good outcomes.
In eight patients with metastatic melanoma (skin cancer), five demonstrated an immune response that produced changes in their tumors, and four achieved full regression, with their growths disappearing, at least for now.
The research, led by Prof. Cyrille Cohen, who heads the Laboratory of Tumor Immunology and Immunotherapy at Bar-Ilan University, provides evidence that personalized medicine — treatment tailored to the specific patient, a hot topic in oncology in recent years — can be effective. The research was conducted in cooperation with scientists at the National Institutes of Health in Bethesda, Maryland.
“On the one hand, we know that cancer is derived from normal cells in the body that undergo DNA changes that we call ‘mutations,’” explained Cohen. “On the other hand, we also know that the body’s immune system is very sensitive and has the capability of distinguishing between normal cells and cancer cells at the molecular level.”
One of the fundamental problems is the difficulty the immune system has in identifying the genetic mutations that cause cancer as abnormal cells that must be fought off, but researchers now believe that at least some T-cells, white blood cells that fight off disease-bearing invaders, can indeed identify the mutations. There are still three major difficulties: The T-cells’ identification abilities are limited, the quantity of the relevant cells produced by the body is relatively low and despite similarities between various types of cancer the body’s responses to cancer are quite individual and are affected by the unique characteristics of each patient’s cancer and immune system.
The researchers scanned the DNA of the eight patients to pinpoint the cell mutations and compare them to the cells of healthy people, discovering numerous mutations, in some cases thousands. Surveying the mutations allowed the researchers to detect cell flaws.
The researchers also took samples of T-cells from both the tumors and each patient’s blood. Using algorithms developed specifically for this purpose, the researchers tried to determine or predict which mutations would be most susceptible to an attack by the immune system. They then tried to identify which of the patient’s own T-cells were likely to do the best job.
“For each patient we came up with 40 to 50 potential targets, points in the genetic mutations that we thought certain T-cells could identify,” said Cohen. After assessing which T-cells would best identify the tumor, they succeeded in isolating them and multiplying them in the lab tens of thousands of times. As a result the chemical preparation of T-cells injected back into each patient contained a much larger quantity of these personalized disease fighters than would occur naturally. As noted, this process proved surprisingly effective.
Cohen stressed that this was a preliminary, preclinical study, conducted on a very small number of patients. These patients will continue to be followed by the researchers.
The focus on encouraging the body’s own immune system to fight cancer cells has generated increasing interest in recent years, and there have been several breakthroughs. It is part of a larger set of biological drugs and treatments to treat cancer based on the study and exploitation of the disease’s own biological mechanisms.
Cohen believes the human body has cells capable of fighting off cancer, but they are few in number and need some assistance.
“These cells don’t just circulate in the area of the growths, but throughout the blood,” Cohen says. “The problem is that in some of the patients we saw that they constitute only 0.002 percent of their blood cells. In our study we presented direct proof that they are in the blood and they can be a source for an alternative immune system that perhaps in the future, together with other treatments, can provide a proper immune response to cancer.”
The research was published in September in the Journal of Clinical Investigation, and presented at the recent meeting of the Society for Immunotherapy of Cancer.