Why is it better to use your own cells for CAR-T cell therapy?

Nature: Why is it better to use your own cells for CAR-T cell therapy? Are CAR-T cells better than autologous T cells or allogeneic? The latest research of the “Nature” sub-issue gives the answer. 

As one of the most popular immunotherapy technologies at present, CAR-T cell therapy has become the mainstay of immunotherapy, and it is supported by immune checkpoint inhibitors (PD-1/PD-L1 inhibitors are one of them). Frontier research field of immunotherapy.

As an innovative immunotherapy technology, CAR-T cell therapy has been known for its ultra-high initial remission rate from the very beginning. Basically, most advanced cancer patients (hematological tumor patients) receiving treatment can achieve effective remission. This data can reach more than 90%, and according to the latest 5-year long-term follow-up data of CAR-T cell therapy published in “NEJM”, the patient’s sustained remission can reach 58% or even 60%. This is for patients with advanced hematological tumors. It has to be said that it is quite gratifying data.

However, the preparation cycle and cost of CAR-T cell therapy are also restrictive factors. The CAR-T cells currently used are mainly extracted and isolated from the patient’s own body, and are generally obtained after the patient is sick. The preparation of CAR-T cells is generally In 2 weeks to 1 month, if the patient’s own T cells have problems, it may lead to poor therapeutic effects of CAR-T cell therapy. Therefore, is it possible to use other people’s T cells for treatment?

Compared with autologous CAR-T cells, T cells in allogeneic CAR-T cells are often donated by healthy donors, so they can be prepared in advance and stand by at any time, thus ensuring the timeliness of treatment and saving part cost. So is it feasible to use allogeneic T cells to prepare CAR-T cells for treatment? Is it really more advantageous than CAR-T cells prepared from autologous T cells?

In the previous article, we explained why autologous CAR-T cells are more advantageous from a technical and theoretical level, and the article published recently in “Nature Reviews Clinical Oncology” brought us the results of clinical trials. . Let us compare the advantages and disadvantages of autologous CAR-T cells and allogeneic CAR-T cells.

First of all, the first point is naturally indisputable: comparison of efficacy. According to the first-stage multi-center allogeneic CAR-T clinical trial data made by Benjamin et al., the data of the allogeneic CAR-T clinical trial of 7 pediatric patients and 14 adult patients showed that the overall response rate of patients It was 67%, and the median sustained response time was 4.1 months; at 6 months, the progression-free survival rate was 27%, and the overall survival rate was 55%. As we mentioned earlier, the initial overall response rate of most autologous CAR-T cell treatments can reach about 90%, and the 5-year sustained remission rate is 58% (data from patients with diffuse large B-cell lymphoma). According to this data, the effect of autologous CAR-T cell therapy is a bit higher.

The second point that needs to be compared is the expansion and detectability of CAR-T cells in the body. We know whether CAR-T cells persist, which is crucial to whether the tumor will relapse later. At this point, the researchers tested allogeneic CAR-T cells: of the 21 patients who received treatment, 3 cases could still detect allogeneic CAR-T cells after 42 days, and only 1 case after 120 days Allogeneic CAR-T cells can still be detected. Correspondingly, as the first marketed CAR-T cell therapy, the median survival time of autologous CAR-T cells used can reach 168 days, and a considerable number of patients can still be detected at the 20th month Autologous CAR-T cells, so in terms of expansion, autologous CAR-T cells have more advantages.

The third point is the comparison of side effects. Compared with autologous CAR-T cell therapy, the incidence and severity of side effects of allogeneic CAR-T cells are higher. As one of the most common side effects, the incidence of cytokine storm (CRS) of allogeneic CAR-T cell therapy reached 91%, and 14% were grade 3 and 4 adverse reactions; in addition, another common side effect neurotoxicity , It also occurs in 38% of patients.

In addition, there is also a very important point is the burden of treatment-we must know that the human body is highly exclusive, which is also one of the functions of the immune system, which is to remove the “foreign” substances that enter the human body, the foreign CAR- T cell is a “foreign body”. Therefore, when infusing allogeneic CAR-T cells, the patient needs to undergo more intense lymphatic dissection to reduce rejection. Therefore, this is also a problem for the patient’s own body. Not a small burden of treatment.

At present, autologous CAR-T cell therapy has more advantages than allogeneic CAR-T cell therapy in terms of efficacy, durability, side effects and treatment burden. Allogeneic CAR-T cell therapy still needs further development. Of course, there are many companies around the world that provide cell cryopreservation services. People can freeze their T cells when they are young and healthy for use in future illnesses. This is also a good way to cope.

In general, allogeneic CAR-T cell therapy has developed rapidly in recent years, but there is still a certain gap compared with autologous CAR-T cell therapy. CAR-T cell therapy technology is also constantly advancing. I believe that with the progress of immunotherapy principles and clinical research, we will hope to see a better cancer treatment landscape.

(source:internet, reference only)

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