Any breakthrough treatment of human disease will ultimately require long-term safety and effectiveness validation to truly benefit patients.

Editor’s note: This article is from Seidt Bio.

Recently, the US FDA has awarded the LN-145 breakthrough therapy for tumor infiltrating lymphocytes (TIL) therapy for the treatment of patients with recurrent, metastatic or persistent cervical cancer after chemotherapy, with the help of “breakthrough therapy”. It is determined that the therapy is expected to be submitted for listing next year and will be approved soon.

TIL therapy was first discovered in the late 1980s. Simply put, TIL therapy is to separate lymphocytes directly from the surgically cut tumor tissue, and then directly transfer the cells back to the patient after amplification in the laboratory. In addition to TIL therapy, the cell immunotherapy currently under study, as well as stem cells, genetically modified CAR-T, CAR-NK, etc., are at the forefront of research. Existing cell therapies have been validated over many years of application or will lead to new breakthroughs in treatment.

Any breakthrough therapy for human disease will ultimately require long-term safety and validation to truly benefit patients. One of them is the CAPRI cell therapy that is currently being used to declare clinical CYRI cell therapy. In the frontier genetic modification technology field, there is also a CAR-T based on humanized CD276 antibody, based on CAR-T and CAR, which are widely developed at present. -NK technology is completely different from many research and development pipelines such as CAR technology. The reason why the clinical application of CAPRI cell therapy is prioritized in many R&D pipelines is precisely because the therapy has accumulated more than 30,000 treatment cases at home and abroad since the first generation of inventions. The safety and effectiveness have been fully verified and can be expected. Clinical effects and new drugs went on the market.

Effect of CAPRI Cell Therapy

Control treatment at several hospitals at home and abroad has proved that CAPRI cell therapy has obvious effects on the average survival cycle and survival rate of various solid tumors. Some published data are as follows:

Non-small cell lung cancer:

潮科技| Cell therapy industry exploration: CAPRI cell therapy

In the Yunnan Provincial Cancer Hospital, 60 patients with non-small cell lung cancer (stage I-IV) were followed up for 12 months, 30 of whom underwent CAPRI cell therapy. Patients randomized to the same tumor stage and the same basic treatment at the same time were randomized. 30 cases were taken as a control groupCompare. Follow-up showed that the average survival time of the CAPRI cell treatment group was 11.9 months, and that of the control group was 10.7 months. The overall survival rate increased from 70% to 93%. X2 = 5.76, P = 0.016.

潮科技| Cell therapy industry exploration: CAPRI cell therapy

Affiliated Hospital of Weifang Medical College conducted follow-up of 50 patients with advanced non-small cell lung cancer (stage IIIB-IV) for 24 months. Among them, 25 patients underwent CAPRI cell therapy + radiotherapy + palliative chemotherapy. Twenty-five patients who underwent radiotherapy plus palliative chemotherapy were compared in the control group. Follow-up showed that the overall progression-free survival rate of the CAPRI cell-treated group was higher than that of the control group (15 months vs 10 months, P=0.025), and the overall survival of the CAPRI cell-treated group was significantly higher than that of the control group (21 months vs 13). Month, P=0.006), the 1-year and 2-year overall survival rates of the two groups were 56% vs 40% and 36% vs 12%, respectively.

Breast Cancer:

潮科技| Cell Therapy Industry Exploration: CAPRI Cell Therapy

Several breast cancer patients (stage I-III) after surgery and basic chemotherapy in the Department of Breast Surgery, Zhongshan People’s Hospital, Guangdong Province, randomized to follow-up for 30 months. Among the 32 patients with CAPRI cell therapy and 32 controls, follow-up showed that the progression-free survival rate was 78.1% in the CAPRI cell-treated group, which was significantly higher than the control-free survival rate of 53.1% in the control group, X2 = 4.255, P=0.039. .

潮科技| Cell Therapy Industry Exploration: CAPRI Cell Therapy

Munich Immunotherapy Center after surgery and basic chemotherapy59 patients with early breast cancer (stage I-III) underwent CAPRI cell therapy and were followed up for 60 months and retrospectively, with early breast cancer patients (stage I-III) with basic treatment regimen. In contrast, the average survival of the CAPRI cell-treated group was higher than that of the control group (59.8 months vs 52.3 months), and the 5-year survival rate of the treatment group was significantly higher than that of the control group (96% vs 75%), X2 = 14.80, P= 0.00012.

潮科技| Cell Therapy Industry Exploration: CAPRI Cell Therapy

The Munich Immunotherapy Center performed CAPRI cell therapy on 46 patients with advanced breast cancer who received chemoradiotherapy (stage IV), and followed up for 60 months and retrospective studies to treat the advanced mammary gland with the same basic treatment regimen. The cancer patients (stage IV) were controls. The average survival time of the CAPRI cell treatment group was significantly higher than that of the control group (53.2 months vs 30.54 months). The 5-year survival rate of the treatment group was significantly higher than that of the control group (72.0% vs 23.5%). , X2 = 34.38, P = 0.0000000044.

Colorectal cancer:

潮科技| Cell Therapy Industry Exploration: CAPRI Cell Therapy

Oncology Department of Weifang Medical College randomly divided 50 patients with colon cancer (stage II-III) and followed up for 24 months. Among them, 25 patients received chemotherapy and CAPRI cell therapy, 25 patients As a control group, only chemotherapy was received. Follow-up showed that the 2-year progression-free survival rate was 52% in the CAPRI cell-treated group and 24% in the control group, X2 = 4.16, P=0.041.

Safety of CAPRI Cell Therapy

According to the statistics of the safety of the therapy in a number of hospitals, the total number of patients who received CAPRI cell therapy was 18 patients who had adverse reactions due to cell therapy.

潮科技 | Cell therapyLaw industry exploration: CAPRI cell therapy

The level of adverse reactions was grade 1, including local skin irritation (1.26%), local swelling and pain (1.68%), chills (0.4%), nausea, vomiting (2.1%), transient fever (2.1%) . Local allergic reactions such as itchy skin and redness disappeared within a few days. The systemic adverse reactions such as nausea, vomiting, and transient fever recovered spontaneously within 4-6 hours. Only one case of hypothermia returned to normal 48 hours after the onset of hypothermia.

潮科技| Cell Therapy Industry Exploration: CAPRI Cell Therapy

What is a CAPRI cell?

CAPRI cells are called Cascade Primed Immune Cells, which are cells in which peripheral blood mononuclear cells are activated and cultured in vitro by the T cell receptor pathway to obtain a specific killing function against tumors. CAPRI cells are mainly composed of CD4+T helper cells and CD8+T killer cells, and also contain a small amount of NK, NKT, and DC cells. CAPRI cells secrete tumor necrosis factor (TNF-α), interferon (IFN-γ), interleukin 2 (IL-2), interleukin-6 (IL-6), etc. An anti-tumor cytokine.

潮科技| Cell Therapy Industry Exploration: CAPRI Cell Therapy

The Mechanism and Characteristics of CAPRI Cell Therapy

1. Tumor killing specificity and potency: MHRI-I and MHC-II antigen-blocking experiments, CAPRI cells are all compatible with MHC, halfThe primary cell killing experiments of coincident and dissimilar tumors, CAPRI cells against MHC all-matched xenogenic tumor cell killing experiments, all proved that CAPRI cells are specific and efficient for tumor killing. Since proteins secreted by tumor cells can be confirmed in the blood, it is feasible to obtain antigenic presenting cells (APCs) to obtain their phagocytic tumor proteins. CAPRI cell therapy is the application of this feasibility, so it is of great significance for the treatment of tumors, prevention of recurrence after tumors and metastatic lesions.

2. High safety: CAPRI cells are activated autologous cells, do not require genetic modification, do not need to recognize the immunogenicity of tumor peptides, are safe to use, have no serious adverse side effects, and are better for patients. Tolerance.

3. Short culture period and strong operability: CAPRI cell culture has the characteristics of short culture time, rapid proliferation rate, and large increase in anti-tumor activity cells.

潮科技| Cell Therapy Industry Exploration: CAPRI Cell Therapy

CAPRI Cell Features

The discovery of tumor vaccines dates back more than 100 years, and it has only been clinically effective for almost 10 years. As we all know, any drug can only stand the test after passing the time verification, and successfully obtain the drug marketing permission, which really benefits the patient. CAPRI cell therapy with high safety and significant efficacy can be the next “breakthrough therapy”. As a biotechnology company based on the present and focusing on the future, the pace of research on the frontiers of Sidet Biotechnology will not stop. The new CAR-T targets such as CD276, which are currently cutting edge research, will become one after another under the verification of time. “Breakthrough therapy.”

At present, Sidet Bio has simultaneously initiated the clinical declaration of CAPRI cell therapy in China and Australia. For the future, Seidt Bio is full of confidence – it has invested nearly 100 million yuan of its own funds, targeting the trillion market of cell therapy. The company intends to declare overseas listing in 2022, and the market value is expected to be no less than US$3 billion in the future. Before the IPO, the company plans to conduct only two rounds of financing, mainly selecting professional investment institutions with industry resources to seek common development.

References:

1. Activated Monocytes Prime Naı ̈ve T Cells Against Autologous Cancer: Vigorous Cancer Destruc