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CAR-T Cell Therapy Project New DC Vaccine Treatment Stem-cell-gene-transformed iNKT Cell Therapy Basic principle of CAR-NK cell therapy

CAR-T Cell Therapy Project

1. Basic principle of CAR-T cell therapy


The CAR-T cell therapy is a gene engineering technology. It first transforms a fragment of scFv, an antibody capable of recognizing a tumor-specific antigen, then integrates the fragment into the transmembrane chain segment consisting of a series of molecules involved in T cell activation such as CD28, 4-1BB and CD3-ζ, forming a recombinant plasmid CAR. The CAR will be transduced into the T cells of a patient and cause them to express CAR. After the “re-coding”, a large amount of tumor-specific CAR-T cells will be generated to attack and eventually ablate the tumor.


2. Development history of CAR-T cell therapy



3. Advantages of CAR-T cell therapy





4. Project Background

April 2015: Completed the construction of the technology platform in Zhangjiang;

September 2015: Held CAR-T Clinical Trial Kick-off Meeting;

October 2015: Realized stable production of the viruses prepared from CAR-T;

December 2015: The first success of CAR-T infusion by Hrain in a patient with B-cell lymphoma;

February 2016: Registered 2 clinical trials on clinicaltrial.gov., reaching 8 in total;

February 2016: The first success of CAR-T infusion by Hrain in a patient with leukemia;

January 2017: The first success of CAR-T infusion by Hrain in a patient with multiple myeloma;

January 2018: The first success of CAR-T infusion by Hrain in a patient with liver cancer;

January 2018: 93 of the 130 enrolled patients received infusion.;

July 2018: Obtained the approval for clinical trials for two anti-human CD19 T cell injections;

August 2018: Started the cooperation with Shanghai First People's Hospital affiliated to Shanghai Jiaotong University - the 4th clinical trial center for registered clinical research projects.


5. R&D Line and Progress:



6. Clinical trials: multiple myeloma, adult and childhood B-cell leukemia, B-cell lymphoma, B-cell lymphoma relapsing after CD22 CAR and CD19 CAR treatment or irresponsive to CD22 CAR and CD19 CAR treatment.


1) Registration: 8 clinical trials have been registered with clinical collaboration centers on ClinicalTrials.gov.


Registration No.:NCT02685670
Project name:Competitive Transfer of αCD19-TCRζ-CD28 and αCD19-TCRζ-CD137 CAR-T Cells for B-cell Leukemia/Lymphoma [MatchCAR]


Registration No.: NCT02903810
Project name:Combination Transfer of αCD19-TCRz-41BB and αCD22-TCRz-41BB CAR-T Cells for B-cell Hematologic Malignancy


Registration No.: NCT03110640
Project name:Anti-CD19 CAR T Infusion Combined with Allogeneic Stem Cell Transplantation for B-cell Leukemia/Lymphoma


Registration No.: NCT02652910
Project name:Memory-enriched CAR-T Cells Immunotherapy for B Cell Lymphoma [MeCAR]


Registration No.: NCT03084380
Project name:Anti-GPC3 CAR-T for Treating GPC3-positive Advanced Hepatocellular Carcinoma (HCC)


Registration No.: NCT03114670
Project name:Donor-derived Anti-CD123-CAR-T Cells for Recurred AML After Allo-HSCT


Registration No.: NCT03093168
Project name:BCMA Chimeric Antigen Receptor Expressing T Cells in Multiple Myeloma


Registration No.: NCT02721407
Project name:Anti-CD22 CAR-T Therapy for CD19-refractory or Resistant Lymphoma Patients [MendCART]


2)A typical case: a 74-year-old patient with diffuse large B-cell lymphoma was enrolled into the MeCAR trial after multiple failures of radiotherapy and chemotherapy; 2 months after the treatment, PET-CT showed that the tumor lesion completely disappeared; and 4 months after the treatment, the fracture caused by tumor invasion to the bone marrow completely healed.



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Cell viability 95.5% CAR-T transfection efficiency 73.7%

Fig. 1. Test before cell packaging for CAR-T infusion --- the viability is 95.5%, and the CAR-T transfection efficiency is 73.7%.

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Baseline before the infusion                                                      2 months after the infusion

Fig. 2. PET-CT imaging comparison of the tumor 2 months after CAR-T infusion with the initial baseline --- the main lesions disappeared. (The shadow at the bladder is generated by metabolism of the contrast agent, not a lesion.)

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Before the infusion                  2 months after the infusion              4 months after the infusion

Fig. 3. Comparison of the non-traumatic fractures caused by bone marrow invasion of tumor cells 2 months and 4 months after CAR-T infusion with the initial baseline --- they are gradually recovered and eventually healed.