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CN-122005815-A - Application of SPRC and PD-1 or PD-L1 inhibitor in preparing lung cancer immunotherapy sensitization medicine

CN122005815ACN 122005815 ACN122005815 ACN 122005815ACN-122005815-A

Abstract

The application provides application of SPRC and PD-1 or PD-L1 inhibitor in preparing lung cancer immunotherapy sensitization medicines, which relates to the technical field of biomedicine, wherein the application confirms that S-propargyl-L-cysteine (SPRC) can exert sensitization effect on the lung cancer resistance of the PD-1 inhibitor through in vitro cell experiments, cell co-culture experiments and in vivo animal experiments, the core mechanism is that 30 mu M SPRC is in a non-cytotoxicity dosage window, and can rely on CSE/H 2 S channel specificity to inhibit IFN-gamma induced STAT1 phosphorylation and PD-L1 up regulation, and IFN-gamma-STAT 1-PD-L1 is a core signal shaft of PD-L1 adaptability up regulation in lung cancer cells, and TNF-alpha has weak induction effect on PD-L1.

Inventors

  • TANG ZHIYUAN
  • ZHU YIZHUN
  • SUN YUENING
  • ZHOU XIAOYU
  • DING QIAN
  • SONG FENGLIANG

Assignees

  • 南通大学附属医院
  • 依诺医药(广东)有限公司

Dates

Publication Date
20260512
Application Date
20260213

Claims (6)

  1. Use of sprc in combination with PD-1 or a PD-L1 inhibitor for the preparation of a medicament for immunotherapy sensitization of lung cancer.
  2. 2. The use of SPRC in combination with PD-1 or PD-L1 inhibitors for the manufacture of a medicament for immunotherapy of lung cancer according to claim 1, wherein the SPRC inhibits IFN-gamma induced phosphorylation of STAT1 and up-regulation of adaptive expression of PD-L1 in lung cancer cells by activating the CSE/H2S pathway.
  3. 3. The use of SPRC in combination with a PD-1 or PD-L1 inhibitor in the manufacture of a medicament for immunotherapy sensitization of lung cancer according to claim 2, wherein the medicament is capable of reducing the rate of depletion of CD8 + T cells in the lung cancer microenvironment.
  4. 4. The use of SPRC in combination with a PD-1 or PD-L1 inhibitor for the manufacture of a medicament for the immunotherapy of lung cancer according to claim 3, wherein the medicament is capable of down-regulating the proportion of PD-1 + 、TIM-3 + cells infiltrated.
  5. 5. The use of SPRC in combination with PD-1 or PD-L1 inhibitors for the manufacture of a medicament for the immunotherapy of lung cancer according to claim 2, wherein the medicament further comprises a pharmaceutically acceptable additional adjuvant.
  6. 6. The use of SPRC as claimed in claim 2 in combination with PD-1 or PD-L1 inhibitors for the manufacture of a medicament for immunotherapy of lung cancer, wherein the SPRC is administered in an effective amount within a non-cytotoxic range, capable of maintaining cell viability at above 85%.

Description

Application of SPRC and PD-1 or PD-L1 inhibitor in preparing lung cancer immunotherapy sensitization medicine Technical Field The application relates to the technical field of biomedicine, in particular to application of SPRC and PD-1 or PD-L1 inhibitor in preparing a lung cancer immunotherapy sensitization medicine. Background In recent years, immunotherapy becomes a breakthrough direction in the field of lung cancer treatment, wherein a PD-1/PD-L1 inhibitor blocks the combination of PD-1 and PD-L1 by virtue of a unique action mechanism thereof, so that the immune escape of lung cancer cells is relieved, the killing effect of body autoimmune cells on the lung cancer cells is activated, and the novel lung cancer treatment composition becomes an important choice of a first-line or second-line clinical treatment scheme. Although the PD-1/PD-L1 inhibitor has been significantly advanced in clinical application and the application range is continuously expanded, a plurality of technical defects to be solved still exist, and the further improvement of the clinical treatment effect is limited, wherein on one hand, only part of patients in clinic respond to the treatment of the PD-1/PD-L1 inhibitor effectively, most of patients have primary drug resistance or have secondary drug resistance in the treatment process, the adaptive up-regulation of lung cancer cells PD-L1 is one of the core reasons for drug resistance, on the other hand, part of patients can have immune related adverse reactions after being used, and the high-efficiency and safe sensitization strategy is lacking at present to improve the treatment response rate of the PD-1/PD-L1 inhibitor and overcome the drug resistance problem, and the existing sensitization agents have the problems of higher toxicity, poor targeting, undefined action mechanism and the like, so that the clinical treatment requirement is difficult to meet. In addition, the PD-1/PD-L1 inhibitor has the limitations of relatively slow onset of action, imperfect biomarker for predicting curative effect, high price and the like, and further restricts the popularization of clinical application, so that the development of a safe and efficient sensitizer for the PD-1/PD-L1 inhibitor has important clinical significance and application value. Disclosure of Invention The application aims to solve the technical problem that the prior art lacks a safe and efficient PD-1/PD-L1 inhibitor sensitizer. In order to achieve the above purpose, the present application provides the following technical solutions: The application also provides application of SPRC and PD-1 or PD-L1 inhibitor in preparing a lung cancer immunotherapy sensitization medicine. Preferably, the SPRC inhibits IFN-gamma-induced STAT1 phosphorylation and up-regulation of adaptive expression of PD-L1 in lung cancer cells by activating the CSE/H2S pathway. Preferably, the agent is capable of reducing the rate of depletion of CD8 + T cells within the lung cancer microenvironment. Preferably, the agent is capable of down-regulating the proportion of PD-1 +、TIM-3+ cells infiltrated. Preferably, the medicament further comprises other auxiliary agents which are acceptable in medicine. Preferably, the SPRC is administered in an amount effective to maintain cell viability at greater than 85% within a non-cytotoxic range Compared with the prior art, the application at least comprises the following beneficial effects 1. The SPRC provided by the application can pertinently inhibit IFN-gamma induced PD-L1 adaptability up-regulation, relieve the inhibition effect of lung cancer cells on immune cells, reduce the CD8 + T cell depletion ratio, form a synergistic effect when being combined with anti-PD-1, effectively improve the lung cancer resistance effect of PD-1 inhibitor, and provide a new solution for the poor treatment effect or drug resistance of PD-1 inhibitor; 2. The application verifies that 30 mu M SPRC is in a non-cytotoxicity dosage window, has no obvious damage to lung cancer cells, and only specifically acts on IFN-gamma-STAT 1-PD-L1 and NF- κB inflammatory pathways, thereby avoiding the extensive damage of the traditional anti-lung cancer drugs to normal cells and improving the safety and tolerance of treatment; 3. The application verifies that the SPRC regulation and control effect depends on a CSE/H2S channel, has strong targeting property, can precisely act on the key links of PD-L1 up-regulation and inflammatory reaction of lung cancer cells, avoids adverse reactions caused by nonspecific intervention, and provides a definite action target for subsequent precise regulation and control; 4. The application verifies that SPRC can inhibit lung cancer progression from the dual angles of anti-inflammation and immune sensitization by inhibiting NF- κB channel activation, down regulating inflammatory factor expression, improving lung cancer inflammation microenvironment and enhancing immune killing ability by cooperating with PD-1 inhibitor,