The first interim results of clinical trials of CRISPR-variant CAR-T therapy to fight against cancer appeared in the USA. This was reported by the press service of the Penn Medical Center at the University of Pennsylvania. Three patients received the injections of edited cells, which took root in their bloodstream and did not cause deterioration. However, the doctors have not yet been able to record the response of patients to therapy.

Despite the fact that CRISPR-editing technologies are devoting more and more scientific research, none of its applications in medicine has yet been officially approved. Only a few clinical trials are known, during which CRISPR-edited cells were injected into the body of patients: some were in China, others in Europe.

Now the pilot tests have reached the United States. At Penn Medical Center, doctors tried CRISPR therapy to fight cancer. In fact, it is a modification of the gene therapy CAR-T, which was approved for use in 2017.

The original CAR-T technique is based on a modification of the T-lymphocyte genome. They are programmed to combat B-lymphocytes, which multiply in some types of blood cancer. For this, a gene that encodes a receptor for the surface protein of B cells is introduced into T cells using viral vectors. Modified cells are propagated and introduced back into the body, where they targeted the tumour.

The CRISPR version of CAR-T is similar to the original only by a general principle. T cells are also taken from patients and edited by their genome. However, in the new method, scientists use CRISPR / Cas9 to remove two genes from T cell DNA: one is the PD-1 protein, which blocks the activity of lymphocytes (the Nobel Prize was awarded for its discovery in 2018). The second is the usual receptor, through which lymphocytes recognize their target. Then, through a viral vector, another receptor gene is introduced into the cells, which binds only to certain proteins on the surface of the tumor. After such triple editing, the T-lymphocyte gains the ability to selectively recognize a cancer cell, and at the same time acquires resistance to its inhibitory effect.

According to scientists, three patients took part in the trial: two with multiple myeloma and one with sarcoma. All three received a single injection of edited cells after a short course of chemotherapy. Later blood tests showed that CAR-T cells had taken root and multiplied in their body. It is too early to judge the effectiveness of the procedure since doctors have not yet noticed the patients’ response to therapy. However, they already say with confidence that there are no side symptoms, which is important – one type of CAR-T therapy has already been defeated due to the sudden death of the patient.

In a conversation with the press service of the medical centre, the researchers mentioned that editing led to the formation of “different variants” of cells, and among them, the most active ones have to be selected. This may mean one of two things: either not all the cells manage to make all three changes in the DNA, or in some, there are inappropriate corrections. Both can be an obstacle to the further development of this method. More precisely, this will be known in a month, when scientists will present the results of their tests.