Tumor immunization method combining with chimeric antigen T cells targeting at PD-1 (programmed cell death protein 1) and EGFR (epidermal growth factor receptor)

Abstract

The invention discloses a tumor immunization method combining with chimeric antigen T cells targeting at PD-1 (programmed cell death protein 1) and EGFR (epidermal growth factor receptor) and also discloses a plasmid vector for implementing the method. In combination with fourth-generation CAR-T (chimeric antigen receptor T) cells targeting at PD-1 and EGFR, a lentiviral vector is used as a CAR-T vector basic structure, and truncated EGFR antibody is selected as a CAR core to give tumor targeted enrichment to play, tumor-killing effect is given to play in conformity with overexpressed immune checkpoint inhibitor PD-1 monoclonal antibody; by constructing the fourth-generation CAR-T vector for co-expressing various regulatory factors such as IL21, CCR4 and Bcl2, the killing, homing and persistent proliferating abilities of CAR-T cells are improved. EP-CAR T (esophageal papilloma chimeric antigen receptor T) cells are treated by transducing patient's autologous T-lymphocytes in vitro, amplifying suitably and transducing back to the patient's body via autologous transfusion, and no reports on similar designs of CAR-T cells are provided at present.

Description

technical field [0001] The present invention relates to a tumor immunization method, in particular to a tumor immunization method combining chimeric antigen T cells targeting PD-1 and EGFR. Background technique [0002] Currently, surgery, radiotherapy, and chemotherapy are the three main methods of clinical treatment for common solid tumors such as lung cancer, liver cancer, and gastric cancer. The shortcomings of this model are obvious: the treatment is extensive, often kills one hundred enemies and damages three thousand, and the improvement of long-term curative effect has been stuck in a bottleneck for a long time. Traditional immunological therapies, including antibodies and cellular immunotherapy (LAK, DC-CIK, TIL), etc., have the inherent advantages of "precise treatment and less side effects", but have disadvantages such as poor universality, weak and unsustainable curative effect. [0003] Since the 21st century, with the rapid development of molecular immunology ...

AI Technical Summary

Problems solved by technology

[0005] However, compared with hematological malignancies, the attempt of CAR-T therapy in the field of solid tumors seems to be struggling

As of the beginning of 2017, as many as 51 CAR-T cell clinical trials have been registered for solid tumors such as lung cancer, gastric cancer, intestinal cancer, and glioma around the world. Targeted genes include CEA, CD171, CD70, EGFR, HER2, GPC3, EpCAM, Mesothelin and MUC1, etc., but so far the efficacy of CAR-T in solid tumors is not satisfactory

The current challenges faced by CAR-T treatment of solid tumors mainly include five aspects: ① Difficulty in T cell transportation (Trafficking): Due to physical barriers such as tissue fibrosis, the infiltration of T cells in solid tumors is obviously less and difficult to infiltrate; ② It is difficult to identify tumor cells: The ideal CAR target should not be expressed in all normal tissues except tumors, but solid tumors are highly heterogeneous, and it is still very difficult to find them; ③CAR-T proliferation and maintenance: Sufficient and durable CAR-T cells are the key to tumor suppression Preconditions; ④Suppression of the immune microenvironment: There are a large number of immunosuppressive factors in the microenvironment of solid tumors, which is not conducive to the survival of CAR-T cells; ⑤Control of CAR-T cells: Effectively controlling the behavior of CAR-T is very important to control the risk of treatment

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