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CN-122005782-A - FBP1 agonist and PD-1/VEGF bispecific antibody composition and anti-tumor application thereof

CN122005782ACN 122005782 ACN122005782 ACN 122005782ACN-122005782-A

Abstract

The invention discloses a FBP1 agonist and PD-1/VEGF bispecific antibody composition and an antitumor application thereof. The invention discovers that the exemestane and the vitamin D have the effect of synergistically inhibiting the growth of lung adenocarcinoma transplantation tumor in lung adenocarcinoma transplantation tumor mice, wherein the exemestane and the vitamin D are a PD-1/VEGF bispecific antibody, and the vitamin D has the effect of promoting the expression of FBP 1. Therefore, the composition of the PD-1/VEGF bispecific antibody, the exemestane and the FBP1 overexpressing agent, the vitamin D has the prospect of being developed into medicaments for treating lung adenocarcinoma.

Inventors

  • LI LIFENG
  • ZHAO JIE
  • YANG YAQI
  • ZHU JIAJIA
  • WU MEI
  • SUN HAOJIE

Assignees

  • 郑州大学第一附属医院

Dates

Publication Date
20260512
Application Date
20260311

Claims (10)

  1. 1. A composition comprising an FBP1 overexpressing agent and a PD-1/VEGF bispecific antibody, wherein the FBP1 overexpressing agent is packaged in admixture with or separately from the PD-1/VEGF bispecific antibody.
  2. 2. The composition of claim 1, wherein the PD-1/VEGF bispecific antibody is exemestane.
  3. 3. The composition of claim 2, wherein the FBP1 overexpressing agent is vitamin D.
  4. 4. The composition of claim 3, wherein the mass ratio of the PD-1/VEGF bispecific antibody to the FBP1 overexpressing agent is 2000:1.
  5. 5. Use of the composition according to any one of claims 1 to 4 for the preparation of an antitumor drug.
  6. 6. The method according to claim 5, wherein the tumor is lung cancer.
  7. 7. The method of claim 6, wherein the lung cancer is lung adenocarcinoma.
  8. 8. The use according to claim 5, wherein the medicament is prepared into a pharmaceutically acceptable dosage form by taking the composition according to any one of claims 1-4 as an active ingredient and using a pharmaceutically acceptable carrier or auxiliary material.
  9. 9. The method according to claim 8, wherein the carrier or adjuvant is solid, liquid or semi-solid.
  10. 10. The method of claim 8, wherein the dosage form is selected from one of an injection, a tablet, a capsule, an inhalant and an oral liquid.

Description

FBP1 agonist and PD-1/VEGF bispecific antibody composition and anti-tumor application thereof Technical Field The invention belongs to the field of medicines, relates to a pharmaceutical composition and application thereof, and in particular relates to an FBP1 agonist and PD-1/VEGF bispecific antibody composition and an anti-tumor application thereof. Background Lung cancer remains one of the leading causes of cancer-related death worldwide, with five-year survival rates of less than 20%. Lung adenocarcinoma (LUAD) is the most common histological subtype, accounting for about half of all lung cancer cases. Despite the great progress made in recent years in the diagnosis and treatment of lung cancer, the prognosis for most patients remains poor, mainly due to late diagnosis and frequent metastasis. This realistic projection suggests that a more effective therapeutic strategy is urgently needed. The advent of Immune Checkpoint Inhibitors (ICIs) has radically altered the therapeutic profile of lung cancer. Through inhibition pathways against apoptosis protein 1/apoptosis ligand 1 (PD-1/PD-L1) or cytotoxic T lymphocyte-associated protein 4 (CTLA-4), ICIs reactivate anti-tumor immune responses and significantly improve clinical outcome in a group of patients, remodelling the LUAD standard of care. However, clinical data indicate that the response rate of immunotherapy is still limited, with only about 20% -30% of patients achieving significant efficacy. Tumor neovascularization is usually unorganized and highly permeable. This abnormal vascular structure can lead to hypoxia within the tumor, which in turn can select for more aggressive tumor cell variants. At the same time, the hypoxic microenvironment can impair the function of immune cells, thereby impairing immune-mediated tumor clearance. Vascular Endothelial Growth Factor (VEGF) is the major regulator of tumor angiogenesis. Fructose-1, 6-bisphosphate 1 (fructise-1, 6-bisphosphatase 1, FBP 1) is one of the key enzymes for gluconeogenesis, which plays an inhibitory role in the process of sugar degradation by catalyzing the hydrolysis of fructose-1, 6-bisphosphate (up-regulating the inhibition of gastric cancer cell growth by FBP1 expression, journal of gastroenterology and liver chemistry, 2018). FBP1 is under-expressed in various tumor cells, and in association with growth and proliferation of tumor cells, activation of FBP1 can inhibit growth and proliferation of tumor cells. Evolvullizumab (Ivonescimab, AK 112) is a PD-1/VEGF bispecific antibody. AK112 competitively inhibits PD-1/PD-L1 interactions, reverses the immunosuppression mediated thereby, and blocks VEGF-A binding to VEGFR2, thereby inhibiting tumor angiogenesis in the tumor microenvironment. Ivonescimab also has significant anti-cancer activity against EGFR mutated locally advanced or metastatic non-squamous non-small cell lung cancer. There is currently no report of the use of FBP1 agonists in combination with PD-1/VEGF bispecific antibodies for the treatment of lung cancer. Based on the latest findings of the applicant of the present application, the present application has been specifically proposed. Disclosure of Invention The present invention aims to overcome the deficiencies of the prior art, and a first aim is to provide a composition of an FBP1 agonist and a PD-1/VEGF bispecific antibody, and a second aim is to provide an anti-lung cancer use of the composition. The above object of the present invention is achieved by the following technical scheme: A composition consisting of an FBP1 overexpressing agent and a PD-1/VEGF bispecific antibody, said FBP1 overexpressing agent being packaged in admixture with or separately from said PD-1/VEGF bispecific antibody. Preferably, the PD-1/VEGF bispecific antibody is exemestane. More preferably, the FBP1 overexpressing agent is vitamin D. More preferably, the mass ratio of the PD-1/VEGF bispecific antibody to the FBP1 overexpressing agent is 2000:1. The application of any one of the compositions in preparing antitumor drugs. Preferably, the tumor is lung cancer. More preferably, the lung cancer is lung adenocarcinoma. Preferably, the medicament takes any one of the compositions as an active ingredient, and is prepared into a pharmaceutically acceptable dosage form through pharmaceutically acceptable carriers or auxiliary materials. More preferably, the carrier or adjuvant is a solid, liquid or semi-solid. More preferably, the dosage form is selected from one of injection, tablet, capsule, inhalation and oral liquid. The beneficial effects are that: The invention discovers that the exemestane and the vitamin D have the effect of synergistically inhibiting the growth of lung adenocarcinoma transplantation tumor in lung adenocarcinoma transplantation tumor mice, wherein the exemestane and the vitamin D are a PD-1/VEGF bispecific antibody, and the vitamin D has the effect of promoting the expression of FBP 1. Therefore, the composition of the PD-1/VEGF