WO-2026091488-A1 - ANTI-TUMOR SHORT PEPTIDE, PHARMACEUTICAL COMPOSITION AND USE THEREOF

Abstract

Disclosed is an anti-tumor short peptide. The short peptide comprises an amino acid sequence shown as Seq ID No: 1; and the N-terminus of the amino acid sequence shown as Seq ID No: 1 is further linked to a cell-penetrating peptide. The short peptide inhibits tumor growth by inducing tumor cell differentiation, the tumor being glioma, and the short peptide being a short peptide derived from LGP2. Also disclosed is an anti-tumor pharmaceutical composition comprising a PD-1 antibody and the short peptide. Also disclosed is the use of the short peptide or the anti-tumor pharmaceutical composition in the preparation of an anti-tumor drug. A novel differentiation therapy route is provided for tumors, especially gliomas.

Inventors

• SHU, Minfeng

Assignees

• 复旦大学

Dates

Publication Date

20260507

Application Date

20250521

Priority Date

20241101

Claims (9)

1. An antitumor short peptide, characterized in that the short peptide comprises an amino acid sequence as shown in Seq ID No: 1.
2. The antitumor short peptide according to claim 1 is characterized in that the N-terminus of the amino acid sequence shown in Seq ID No: 1 is further connected to a membrane-penetrating peptide.
3. The antitumor short peptide according to claim 2 is characterized in that the amino acid sequence of the membrane-penetrating peptide is as shown in Seq ID No: 2.
4. The antitumor short peptide according to any one of claims 1-3 is characterized in that the short peptide inhibits tumor growth by inducing tumor cell differentiation.
5. The antitumor short peptide according to any one of claims 1-3 is characterized in that the tumor is a glioma.
6. The antitumor short peptide according to any one of claims 1-3 is characterized in that the short peptide is a short peptide derived from LGP2.
7. An antitumor pharmaceutical composition, characterized in that it comprises a PD-1 antibody and a short peptide as described in any one of claims 1-6.
8. The use of the short peptide according to any one of claims 1-6 in the preparation of an antitumor drug or in the treatment of tumors.
9. The use of the antitumor pharmaceutical composition of claim 7 in the preparation of an antitumor drug or in the treatment of tumors.

Description

A short antitumor peptide, pharmaceutical composition and its application Technical Field This invention relates to the field of biomedicine, and in particular to an anti-tumor short peptide, a pharmaceutical composition, and its application. Background Technology Differentiation therapy is an innovative treatment strategy that inhibits malignant proliferation by reactivating the differentiation potential of cancer cells, promoting their development towards a mature state. Unlike traditional cytotoxic therapy, this approach does not directly kill cancer cells but reduces their tumorigenicity by altering their differentiation state. Due to its fewer side effects, limited impact on normal cells, and long-lasting efficacy, it has attracted considerable attention in recent years. The earliest successful case came from the application of all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL). This therapy, by degrading the PML-RARα fusion protein, relieved the differentiation arrest of leukemia cells, significantly improving patient prognosis. Currently, with the development of molecular biology techniques, differentiation therapy is gradually revealing its potential new targets in the treatment of malignant tumors and is increasingly being applied to solid tumors such as neuroblastoma and hepatocellular carcinoma. However, the therapeutic effects on solid tumors and the specific mechanisms of differentiation induction remain unclear. The RIG-I-like receptor family (RLRs) includes retinoic acid-induced gene-I (RIG-I), melanoma differentiation-associated receptor 5 (MDA5), and Laboratory Genetics and Physiology 2 (LGP2). They interact with exogenous RNA, causing conformational changes. MDA5 and RIG-I, upon sensing non-self RNA, expose their CARD domains. The exposed CARD interacts with the CARD domain of the mitochondrial antiviral signaling protein (MAVS), promoting the activation of transcriptional regulators including IRF-3 and NFκB, leading to the transcription of type I interferon (IFN) and IFN-inducible genes (ISGs), which participate in the immune response to viral infection. IFN and ISGs not only affect viral replication but also have a direct tumor-killing effect. Although LGP2 can bind to RNA and its binding is stronger than that of MDA5 and RIG-I, it lacks a CARD domain or other signal transduction domains and cannot transmit signals, thus failing to directly interact with the adaptor protein MAVS to induce the production of IFN and inflammatory factors. The function of LGP2 in immune responses remains controversial. Numerous studies have shown that LGP2 promotes MDA5 antiviral signaling. LGP2 is primarily involved in innate and antiviral immunity, but its role in tumors has not yet been reported. Summary of the Invention The technical problem to be solved by the present invention is to provide an anti-tumor short peptide, a pharmaceutical composition and its application. To solve the above-mentioned technical problems, the present invention adopts the following technical solution: On one hand, the present invention provides an antitumor short peptide comprising an amino acid sequence as shown in Seq ID No: 1. As a further improvement of the present invention, the N-terminus of the amino acid sequence shown in Seq ID No:1 is also connected to a membrane-penetrating peptide. Furthermore, the amino acid sequence of the transmembrane peptide is shown in Seq ID No: 2. Furthermore, the short peptide inhibits tumor growth by inducing tumor cell differentiation. Furthermore, the tumor is a glioma. Furthermore, the short peptide is a short peptide derived from LGP2. On the other hand, the present invention also provides an antitumor pharmaceutical composition comprising a PD-1 antibody and the aforementioned short peptide. Furthermore, the present invention also provides the application of the above-mentioned short peptide in the preparation of antitumor drugs. In another aspect, the present invention also provides the use of the above-mentioned antitumor pharmaceutical composition in the preparation of antitumor drugs. This invention investigates the antitumor activity of the aforementioned short peptide (H1), examining its effects on the survival of glioma cell lines U87MG and T98G, its influence on glioma organoid growth and clonogenic capacity, and its effect on inducing the expression of differentiation markers. Subsequently, tumor growth was observed in an experiment involving intracranial implantation of gliomas in BALB/c nude mice. The results indicate that H1 can be used as a short peptide to inhibit tumor growth and induce differentiation. Further experiments show that the H1 short peptide can enhance the efficacy of PD-1 antibody therapy and can be used in combination for antitumor treatment. This invention provides a novel differentiation therapy approach for tumors, especially gliomas. Attached Figure Description II. Experimental Results: The above is merely an overview of the techni