Solid tumors, developed a new method of treating them with Crispr-Cas

Solid tumors

Modifying, thanks to Crispr-Cas, immune cells to treat solid tumors in a more specific way: this is what a small clinical study coordinated by the University of California at Los Angeles, in the United States and published in the journal Nature, seems to promise. In fact, scientists used Crispr-Cas genome editing technology to insert specific genes into T lymphocytes of cancer patients and allow the immune system to selectively target cancer cells, increasing the effectiveness of immunotherapy. This is the first time that the feasibility of such an approach has been demonstrated, which has made it possible to treat sixteen patients with different types of solid tumors, including that of the colon, breast and lungs. According to the authors, this technique, which combines two very hot areas of cancer research, that of gene editing and that of immunotherapy, is a further step towards increasingly personalized anticancer treatments.

A hot field of anti-cancer research

In reality, the use of Crispr-Cas (the molecular technique that allows you to modify specific portions of a cell's genome) is not entirely new in newly developed anti-cancer therapies: how we told you here, genomic editing technology has already been tested in humans to remove some genes in the immune cells of cancer patients, in order to make them more reactive against cancer. In addition, T lymphocytes specifically engineered against cancer cells, called Car-T cells, have been approved for the treatment of certain lymphatic and blood cancers for some years. In short, this sector of anti-cancer research, which combines immunotherapy and genetic modification techniques, is in constant ferment.

Therefore, the authors of the study decided to verify the feasibility of using Crispr-Cas not only to remove certain genes from immune cells, but also to insert new ones, reprogramming them in order to make them recognize specific mutations of cancer cells in patients with solid tumors and thus more effectively target the response against them. The human immune system, in fact, has proteins on the surface of T lymphocytes that selectively bind to cancer cells, distinguishing them from healthy ones, so as to target only what constitutes a threat to the body. These proteins, called T receptors, are different for each patient, as most of the mutations present in cancer cells, while considering the same type of cancer, vary from person to person.

The study and future perspectives

The researchers then isolated immune cells from the blood of 16 people with solid tumors (including colon, breast and lung cancer) which possessed the T receptors selectively directed against the cancerous mutations that allowed to specifically recognize the tumor, for a total of 175 different immune receptors. By applying Crispr-Cas technology, they then inserted genes that encoded previously isolated immune receptors into T lymphocytes.

"This is a step forward in the development of a personalized cancer treatment, in which immune receptors that specifically recognize mutations in the patient's cancer are used for therapy," said Antoni Ribas, author of the study. "Developing a personalized treatment would not have been feasible without the ability to use the Crispr technique to replace immune receptors in cell preparations in a single step".

Subsequently, the cells engineered in this way were reinfused in patients, in whom in a short time they have become the dominant population of immune cells, often representing more than 20% of the white blood cells present in the vicinity of the tumor. One month after treatment, in five of the participants the tumors did not grow further and only two patients had side effects related to the therapy. The efficacy results might seem rather modest, but the researchers purposely used relatively small doses of engineered T cells to determine if the approach was safe: now that its safety and feasibility has been established, they would like to experiment with higher doses and design cells. T that not only recognize tumor mutations, but are also more active against tumors.