Application of aim2 in the preparation of drugs for reducing the toxic and side effects of car-t therapy
A technology of AIM2 and toxic and side effects, which is applied in the direction of drug combination, antineoplastic drugs, biological testing, etc., to achieve the effect of alleviating neurotoxicity and reducing toxic and side effects
Active Publication Date: 2022-06-03
江苏集萃崛创生物科技研究所有限公司
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Problems solved by technology
Through the study of the mechanism of IL-1β induced by CAR-T cell therapy, this application found that knocking down the expression of AIM2 in macrophages can significantly inhibit the increase of IL-1β in the culture supernatant induced by co-culture, from the existing According to research, the application of AIM2 in the preparation of drugs that reduce the toxic side effects of CAR-T treatment has not been reported
Method used
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Embodiment 1
[0058] The THP-1-induced M2 macrophages were used as a macrophage model. Co-culture will be carried out, after 24h, the culture will be collected
[0060] (2) After collecting the supernatant, place the 6-well plate on ice, wash the adherent macrophages twice with PBS, and discard the washing solution. join in
[0065] (7) Take out-20 ℃ of frozen samples, boil at 100 ℃ for 5min in a metal bath. Subsequently, 3000rpm, 5min, centrifuged;
[0068] (10) closed, after the transfer was completed, the NC membrane was taken out, placed in 5% skim milk, at room temperature, and closed on a horizontal shaker for 1 h.
Embodiment 2
[0080] (2) Infect the control lentivirus and the lentivirus carrying AIM2 shRNA, and calculate the required virus dosage according to MOI=30.
[0085] (7) After 24 hours, the cell lysates of the cells in each well were collected, and the knockdown efficiency of AIM2 was detected by Western Blot.
[0086] The M2-type macrophages knocked down AIM2 were co-cultured with CD19 CAR-T and tumor cells, and after 24 h, collected
Embodiment 3
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The invention discloses the application of AIM2 in the preparation of drugs for reducing the toxic and side effects of CAR-T treatment. The present invention found that among the four inflammasomes involved in the release of macrophage IL-1β induced by CAR-T treatment, only the expression of AIM2 was significantly up-regulated. For further verification, the present invention constructed a THP-1 cell line that knocked down AIM2 and applied it Thalidomide, an inhibitor of AIM2, was found, and the results showed that knocking down the expression of AIM2 reduced the release of IL-1β induced by CAR-T treatment, and the application of AIM2 inhibitors could reduce the release of IL-1β induced by CAR-T treatment. This further demonstrates the important role of inflammasome AIM2 in the release of IL-1β from macrophages triggered by CAR-T treatment. The present invention discovers for the first time that the agent that inhibits the expression of AIM2 has potential application value in reducing the toxic and side effects of CAR-T treatment.
Description
Application of AIM2 in the preparation of drugs for reducing the toxic and side effects of CAR-T therapy technical field The invention belongs to the technical field of biomedicine, specifically, relate to the new purposes of AIM2, namely AIM2 reduces in preparation Application of CAR-T in the treatment of toxic and side effects. Background technique Chimeric antigen receptor (CAR) modified T cell immunotherapy (Chimeric antigen receptor T-cell, CAR-T) is a new type of precise and efficient tumor immunotherapy Law. CAR-T cell therapy is to collect T cells from the peripheral blood of patients or donors, and then genetically modify them. CAR gene is introduced into T cells to express specific receptors to bind to specific tumor-associated antigens. After extensive expansion in vitro, Infused back into the patient, these CAR-T cells specifically bind to tumor-associated antigens in vivo and transmit signals to the cells In vivo, T cells are activated to proliferat...
Claims
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IPC IPC(8): A61K45/06A61K39/00A61P35/00A61P25/00C12Q1/6883G01N33/68
CPCA61K45/06A61K39/0011A61P35/00A61P25/00C12Q1/6883G01N33/68A61K2039/5158C12Q2600/158C12Q2600/136G01N2500/04A61K2300/00
Inventor 施明鲍顺顺郑骏年刘丹徐溪悦赵璇李思瑾马文
Owner 江苏集萃崛创生物科技研究所有限公司