Nature sub -magazine: Orr reached 48.6%!Is CAR-T the era of physical tumor?

*For medical professionals for reading reference

Dr. Qi Changsong interpreted the results of the CT041 research results with CAR-T to treat the prospect of physical tumor

CAR-T cell therapy has excellent efficacy in blood system tumors. Among them, CAR-T cell therapy treats the 4-year total survival (OS) rate (OS) rate of 44%. However, in solid tumors, due to lack of good antigen targets and heterogeneity of solid tumors, CAR-T cell therapy progresses slowly.

A few days ago, the team of Professor Shen Lin at Peking University Cancer Hospital announced the mid-term results targeting Claudin18.2 CAR-T cells (CT041) to treat digestive system tumor 1 test in Nature Medicine (IF: 53.44).

Among the 37 patients with advanced digestive system tumors in the group, the objective relief rate (ORR) and the disease control rate (DCR) of CT041 were 48.6%and 73.0%, respectively; the ORR and DCR in patients with gastric cancer reached 57.1%and 75.0, respectively. %.

The first author of the "Medical Tumor Channel" and Dr. Qi Changsong of the Peking University Cancer Hospital analyzed the outlook of the research results and CAR-T cell therapy in the field of physical tumor.

CAR-T cell therapy is hoped to enter the physical tumor?

The excellent curative effect of CAR-T cell therapy in the blood system tumor gives people imagination, and whether CAR-T cell therapy can be further used in solid tumors has always been a hot issue for tumor doctors.

CT041 showed up to 48.6%of ORR in the digestive tumor, which was undoubtedly opened a window for car-T cell therapy into a physical tumor.

In this regard, Dr. Qi Changsong said: "At present, this study should be the best-based physical tumor CAR-T clinical trial. It should be noted that the main tumor we said is relative to the vicious tumor of the blood system, but In fact, it is limited to the digestive tumor. "

CAR-T cell therapy developed in solid tumors is the most difficult thing is the recognition of the ideal target antigen. Blood malignant tumors usually express a single, tumor special antigen, and solid tumors have significant heterogeneity.

Claudin18.2 In the digestive system tumor, especially gastric cancer, pancreatic cancer, biliary system tumors, and part of colorectal cancer. On the other hand, in normal physiological state, Claudin18.2 is only expressed in the differentiated epithelial cells on the gastric mucosa, while no other health tissue is expressed.

Therefore, Claudin18.2 has become an ideal target antigen for CAR-T cell therapy to treat digestive tumors. "However, Claudin18.2 is low in other physical tumors and does not even express it. Therefore, CT041 does not currently have the conditions to promote other tumors." Dr. Qi Changsong said.

Dr. Qi Changsong emphasized: "Most of the patients in the study group are patients with gastric cancer. CT041 treats gastric cancer. Whether it is short -term efficacy or long -term survival data, it has made great breakthroughs compared to traditional therapies."

Compared with other antitumor treatment,

What are the differences between car-T cell therapy?

The biggest feature of CAR-T cell therapy is "personalized customization". During the treatment of CAR-T cells, monocytes need to be collected for patients and genetically modify them. The reconstructed CAR-T cells will return to the patient's body, expand and kill the tumor in the body.

Compared to the development of other drugs, the two characteristics of CAR-T cell therapy are: ① waiting period; ② the treatment of treatment for a long time.

"Car-T cell therapy is not a 'spot type' treatment method. It takes at least 2-3 weeks to prepare CAR-T cells, and other drug treatment does not need to wait for so long." The patient's tumor may progress rapidly, causing them to lose the opportunity to follow the treatment. At this time, we can choose to make a bridge for patients to prevent rapid tumor progress. "

"On the other hand, traditional therapy needs to be continuously taken or intravenous, and CAR-T cell therapy requires 1 to 2 times to lose to achieve better curative effects. CAR-T cells that are lost will be expanded in the body and continued to continue Playing the role. In the ideal state, the loss may be able to achieve a few months, or even a few years of continuous relief. At the same time, patients do not need to frequently come to the hospital for follow -up treatment. "

CAR-T cell therapy is used in physical tumors,

What else should I do?

CT041 showed an exciting effect in clinical studies in Phase 1. However, it is widely used in clinical exploration.

Dr. Qi Changsong said that the current clinical trials in the first phase of the first phase of the group have only entered the group. Although the effect is very good, it still needs to verify the efficacy and safety of CT041 among larger sample groups.

In addition, the first phase study of CT041 is a clinical trial of one-arm open-all patients-all patients receive CAR-T cell therapy. Therefore, its evidence -based medical evidence level will be relatively low. At present, we are conducting a strict random control clinical trial, comparing the efficacy and safety of the current traditional therapy.

In addition to these two directions, Dr. Qi Changsong believes that these directions are worth exploring:

CAR-T cell therapy is applied to the earlier line crowd

This study is basically the last -line treatment crowd of conventional treatment failure. As an immunotherapy, CAR-T cell therapy is closely related to the patient's immune system function. Compared with the last crowd, the immune system of patients with early-line tumors is better. At this time, the efficacy of CAR-T cell therapy may also be better. CAR-T cell therapy for combined treatment

Joint treatment is the exploration direction of CAR-T cell therapy to treat physical tumors. CAR-T cell therapy is progressing slowly in the field of solid tumors, and the current data shows that it cannot achieve the good effect of blood system tumors. CAR-T cell therapy combined with, immune, and even emerging tumor viruses and therapeutic tumor vaccines may have a synergistic effect of 1+1 & 2.

Expert Introduction

Dr. Qi Changsong

The attending physician of the Department of Gastroenterology at Peking University Cancer Hospital, Doctor of Medicine

Member and Secretary of the Chinese Society of Clinical Oncology (CSCO) Gastrointestinal Gastrointestinal Tumor Committee

Member of the Youth Expert Committee of the China Clinical Oncology Society (CSCO)

Secretary -General of the Society of Gastric Cancer Prevention and Treatment of the Beijing Cancer Prevention and Treatment Society

Members of the Statistics Group of the China Clinical Oncology Society (CSCO) Youth Committee

"Tumor Comprehensive Treatment Electronics Magazine"

Mainly engaged in immune therapy, comprehensive diagnosis and treatment of gastrointestinal tumors, transformation of peritoneal metastatic cancer, individual chemotherapy of GIST, and precise treatment of digestive tumors under NGS guidance.

The first release of this article: the medical world tumor channel

Author: oolong tea

Audit expert: Peking University Cancer Hospital Qi Changsong

Editor in charge: Sweet

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