Vitamin D3 or its active form 1α,25(oh) 2 d 3 Application in inhibiting the expression of PD-1
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A technology of PD-1 and vitamins, applied in the field of biomedicine, can solve the problems of not finding screening methods, affecting the effect of PD-1 antibodies, and large toxic and side effects, and achieve good tolerance, enhanced function, and no toxic and side effects.
Active Publication Date: 2021-07-27
北京德衍科技有限公司
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Repeated use of PD-1 antibody will produce anti-antibody, which will seriously affect the effect of PD-1 antibody
However, the research and development of small molecule inhibitors of PD-1 is less, the main reason is that no effective screening method has been found so far, and in addition, the potential toxic side effects of artificially synthesized compounds on the body are also relatively large
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Embodiment 1
[0050] 1α,25(OH) 2 D. 3 (Calcitriol) has the following structural formula:
[0051]
[0052] The above compounds are used as PD-1 inhibitors. This compound is commercially available from Sigma Corporation.
Embodiment 2
[0053] Example 2: Expansion of Vγ9Vδ2 T cells
[0054] The normal human blood buffy coat was separated from the Guangzhou Blood Bank Center. The separation solution (ficoll) was purchased from GE Healthcare, and the gradient centrifugation (600g, 30min, centrifugation conditions: up to 6 down to 2), and the obtained peripheral blood mononuclear cells were selected Sexual expansion culture (culture conditions: on the 0th day, Zol phosphoric acid (Zol, purchased from Sigma Company) 30-50 (μM), the concentration used in this implementation is 40 (μM), recombinant human interleukin 2 (IL-2), 40ng / mL, 1α,25(OH) 2 D. 3 The addition amount is 50 (nmol / L); on the third day, the culture medium is changed without adding Zol, and the recombinant human interleukin 2 is changed to 10ng / mL, 1α,25(OH) 2 D. 3 The amount added was 50 (nmol / L); the ratio of Vγ9Vδ2 / CD3 was detected by flow cytometry on the 12th day. The result is as figure 1 As shown, the results showed that Vγ9Vδ2 T cells ...
Embodiment 3
[0055] Example 3: Protein lysis (RIPA) was performed on the Vγ9Vδ2T cells in Example 2, and 20ug was used for protein gel electrophoresis to detect the protein level of PD-1, and actin was used as an internal reference. The result is as figure 2 As shown, the results show that 1α,25(OH) 2 D. 3 It has a good inhibitory effect on PD-1 of Vγ9Vδ2T cells.
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Abstract
The invention discloses vitamin D3 or its active form 1α, 25(OH) 2 D. 3 Application in inhibiting the expression of PD‑1. 1α,25(OH) 2 D. 3 VDR can inhibit the expression of PD-1 on the surface of activated CD8 T cells and γδ T cells. At the same time, VDR can also promote the expression of Blimp1. Blimp1 can effectively inhibit the expression of PD-1, thereby enhancing the tumor killing function of T cells. 1α,25(OH) 2 D. 3 It can also be used in combination with cytokines such as IL-2 and IL-15, which can more effectively reduce the expression of immune cell PD-1, and at the same time promote the expression of CD28, thereby enhancing the killing function and metabolic function of T cells and maintaining the immune function of T cells. Steady state, and because vitamin D3 has minimal toxic side effects and a wide tolerance range, it can promote T cells to secrete type I interferon. Therefore, it can be used in the treatment of various diseases, including tumors and infectious diseases.
Description
technical field [0001] The invention belongs to the field of tumor immune cell therapy and antiviral biomedical technology, in particular to vitamin D3 or its active form 1α,25(OH) 2 D. 3 Application in inhibiting PD-1 expression. Background technique [0002] Tumor is one of the major diseases that threaten human health and life at present. Tumor-based treatments mainly include surgical therapy, chemotherapy, radiotherapy and immunotherapy. At present, immunotherapy is in full swing and occupies a large market share. In the process of tumor immunotherapy, currently the world's major pharmaceutical companies mainly use PD-1 monoclonal antibody, among which, the precious Opdivo (El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH Rd, Meyer T, Kang YK, Yeo W, Chopra A, Anderson J, Dela Cruz C, Lang L, Neely J, Tang H, Dastani HB, Melero I..Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-la...
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