At present, with the change of CAR-T algebra, CAR-T has obvious improvements in proliferation and cytokine release. This technology has finally broken the ice, and more and more clinical trials have begun to try to use CAR-T for solid tumors. Treatment, patients with advanced solid tumors ushered in a warm spring!

Typical antigen targets include:

Mesothelin, used to treat mesothelioma, pancreatic cancer, ovarian cancer, lung cancer; CEA, used to treat lung cancer, colon cancer, stomach cancer, breast cancer and pancreatic cancer; MUC-1, used to treat liver cancer, lung cancer , Pancreatic cancer, colon cancer, gastric cancer; GPC3, for the treatment of liver cancer; EGFRvII, for the treatment of gliomas, head and neck tumors; B7-H3, for the treatment of Ewing’s sarcoma, rhabdomyosarcoma, nephroblastoma, nerves Blastoma and medulloblastoma and brain stem tumors (DIPG), which are particularly difficult to treat;

PSMA, used for prostate cancer, etc .;

Claudin 18.2, used for gastric cancer, pancreatic cancer, etc.

01 、 Mesothelin CAR-T

Mesothelin is a cell surface glycoprotein that is highly expressed in various tumors, such as malignant pleural mesothelioma, pancreatic cancer, ovarian cancer and some lung cancers, and is lowly expressed on the surface of normal pleura, peritoneum and pericardium. CAR-T cells against mesothelin have potential antitumor effects.

The latest results of mesothelin CAR-T therapy published by the University of Pennsylvania at the American Society of Clinical Oncology in 2019 show that a total of 6 patients with refractory metastatic pancreatic duct adenocarcinoma were successfully enrolled, and all patients have received 2 or more Multiple treatments. These patients were infused with mesothelin CAR T cells 3 times a week for a total of 9 doses. The results showed that there were 2 patients with stable disease, and their progression-free survival time was 3.8 months and 5.4 months.

Therefore, this novel therapy is biologically active in patients with pancreatic cancer, and this study is still in clinical trials (NCT03323944).

02 – B7-H3 “Pan cancer” CAR-T

The team of Professor Majzner from Stanford Medical College has developed a new generation of CAR-T therapy for solid tumors. This special CAR T-Cell therapy is hailed as one of the most promising therapies because it targets a B7-H3, a high level of antigen present in many solid tumors, including some childhood cancers.

They screened 388 children’s tumors for testing. The results showed that B7-H3 was present in 84% of the samples (tumor cells). B7-H3 content was very high in 70% of the samples. These include Ewing’s sarcoma, rhabdomyosarcoma, nephroblastoma, neuroblastoma and medulloblastoma, as well as brain stem tumors (DIPG) that are particularly difficult to treat.

Subsequently, Professor Majzner and his team formed a new generation of CAR-T cells-B7-H3 CAR-T through gene editing technology.

Immediately afterwards, the researchers could not wait to start the experiment on mice. They transplanted human tumor cells into mice to form multiple mouse models of childhood cancer. These mouse models were given B7-H3 CAR T-Cell therapy and CD-19 CAR-T control group, respectively.

Everyone was stunned! Professor Majzner said: “The tumor has just disappeared.”

03, claudin18.2 CAR-T

In the past two years, solid tumors in our country have achieved world-renowned achievements, and the world’s first solid tumor CAR-T therapy targeting Claudin 18.2 has been developed.

Claudin18.2 (CLDN18.2) is a gastric-specific membrane protein and is considered a potential therapeutic target for gastric cancer and other cancer types. Based on this, Chinese researchers have developed the world’s first CAR-T cells against Claudin 18.2.

At the 2019 ASCO Annual Conference, clinical data updates of CAR-Claudin 18.2 T cells for gastric / pancreatic cancer showed that targeted claudin 18.2 CAR T cells were used to treat 12 cases of metastatic adenocarcinoma (7 cases of gastric cancer and 5 cases of pancreatic cancer). A serious adverse event, treatment-related death, or severe neurotoxicity occurred.

Among 11 evaluation objects:

1 case (gastric adenocarcinoma) completely relieved;

3 cases (gastric adenocarcinoma

2 cases of pancreatic adenocarcinoma, 1 case) partial remission;

5 cases were stable;

2 cases progressed;

The overall objective response rate was 33.3%.

Moreover, CAR-Claudin 18.2 T cells for preclinical research on gastric cancer have shown that CAR-T cells targeted to Claudin 18.2 can completely eliminate gastric tumors in mouse models without off-target toxicity.

The good news is that this trial has been pioneered by the Department of Gastroenterology and Oncology at Peking University Cancer Hospital, which is famous for gastrointestinal tumors in China, to evaluate autologous humanized anti-claudin 18.2 chimeric antigen receptor T cells in advanced solid tumors. Safety and efficacy. Entry criteria (partial)

1. Age 18 to 75 years, male or female;

2. Subjects with pathologically confirmed solid tumors (ie advanced gastric cancer, esophagogastric junction cancer, and pancreatic cancer) who have failed standard treatment;

3.Claudin 18.2 IHC staining positive;

4.Expected life> 12 weeks;

FAQ’s on CAR T-Cell therapy

Is Car-T cell therapy available? What cancer is mainly treated

A CAR-T cell immunotherapy has been approved by the US FDA for the treatment of leukemia and lymphoma. However, the treatment of solid tumors has not yet been approved and is currently in clinical trials

Can Car-T cells treat gastric cancer?

Answer CAR-T for gastric cancer is currently undergoing clinical trials in Beijing Cancer. Patients are required to use tissue sections within one year to the experimental group for specific target detection. If the test result is positive, then

Is there a clinical trial of Car-T cells for gastric cancer ?

A There are domestic clinical trials of CAR-T for gastric cancer, which is carried out at Peking University Cancer Hospital. Patients are required to have pathological tissue sections within one year for screening of specific targets. Currently enrolled patients