Making T-cells Fight Tumors

A new research from Rockefeller University shows that our immune system cells can detect and destroy cancerous tumor cells in breasts and ovaries. The protein that detects the cancerous cells was identified and can be used in future immunity-based therapeutic drugs.
Dr. Robert B. Darnell (Credit: Rockefeller University /Dirk Westphal)
Dr. Robert B. Darnell
(Credit: Rockefeller
University/Dirk Westphal)

Already half a century ago, it was hypothesized that the immune system has a role in detecting and destroying cancer cells. The idea was put forward by American and Australian scientists in 1957. They suspected that everybody develops tumors but that the immune system seeks and destroys these cells on a daily basis. This concept was proven true several times in the past, and TFOT reported how joint research of scientists from the Wake Forest University School of Medicine and the Ludwig Institute for Cancer Research in New York, led to the discovery that some individuals have a better natural immune response to cancer cells than others. In the recent Rockefeller University research, scientists actually identified the specific immune cell, and the protein expressed in it, responsible for detecting gynecological cancers. This achievement marks yet another step forward in the understanding of our immune system’s anti-cancer mechanisms.

The scientists’ main problem in proving the hypothesis was finding a case in which the immune system responded to tumor cells, since no symptoms are shown. The solution came from patients of an autoimmune neurodegenerative disease called paraneoplastic cerebellar degeneration (PCD), in which T-cells attack neurons in the brain. PCD is caused as a result of induction of T-cells that recognize an antigen called cdr2, an antigen present in gynecological cancer cells. As the immune system recognizes the tumor, it generates specific T-cells which then attack the neurons. PCD patients often suffer from gynecological cancer in early stages.

By screening the T-cells taken from PCD patients, the protein that detects cdr2 was found. In order to identify the specific protein, samples of PCD patients’ T-cells were screened for highly expressed genes. In a supporting experiment, the team screened T-cells  of mice that were injected with an epitope (part of a protein) of cdr2. Some candidates were then chosen from the highly expressed set of genes and eventually, a single protein was proven to be active against the antigen cdr2. The scientists proved this by injecting the protein into a normal T-cell, which consequently was able to kill cdr2-expressing tumor cells. The protein identified by the scientists is able to transform a normal T-cell into a tumor detecting and destructing T-cell.

The Rockefeller University team’s findings can open a new therapeutic pathway  for fighting breast and ovarian cancers. Some experts believe that using antibodies is preferable over carrying out surgery or using radio therapy/chemotherapy. Exploiting the immune system for this cause is considered safe and free of side-effects. However, caution should be taken before applying the method to avoid causing auto-immune diseases such as PCD. The researchers say that in normal cases it is not likely that PCD should develop, because the T-cells usually do not react to such low levels of cdr2 present in the neurons. This research has demonstrated that our immune system can be used to fight not only bacteria or viruses but also cancer cells.

TFOT recently covered several other cancer related developments, including a novel jet injections technology developed by scientists at Queen’s University in Belfast, which can help treat skin cancer, and a method of killing cancer cells using an electrical field, developed at the Technion Institute in Israel.

More information about the research can be found in the Rockefeller University news release.