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.
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.
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%.
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.)
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.