Antigen capture nanoparticles and formulations for immunotherapy

By enhancing the presentation of cancer-specific antigens by immune cells after radiotherapy with novel antigen-capturing nanoparticles (ACNPs) and combining them with adjuvants, the problem of insufficient synergy between radiotherapy and immunotherapy was solved, achieving more effective cancer treatment and enhanced immune response.

CN120659602AInactive Publication Date: 2025-09-16ARCHIMMUNE THERAPEUTICS INC
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Patent Information

Application Number
CN202480011028.7
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Priority Date
2023-02-06
Filing Date
2024-02-06
Publication Date
2025-09-16
Estimated Expiration
Not applicable · inactive patent

AI Technical Summary

Technical Problem

In existing immunotherapy, the synergistic mechanism of radiotherapy and immunotherapy has not been fully utilized, resulting in limited abscopal effects. Only 10-20% of patients obtain lasting benefits, and there is a lack of effective methods to enhance abscopal effects.

Method used

Develop novel antigen capture nanoparticles (ACNPs) that enhance the presentation of cancer-specific antigens by immune cells after radiotherapy by combining a PLGA core with a protease-sensitive protein sequence, and combine with adjuvants such as small molecules and double-stranded RNA molecules to enhance the immune response.

Benefits of technology

Significantly improve the synergistic effect of radiotherapy and immunotherapy, enhance the abscopal effect, improve the cancer treatment effect, enhance the immune response, and improve the patient's treatment response rate.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention provides novel antigen capture nanoparticles (ACNPs) and pharmaceutical formulations containing such ACNPs. Also provided herein are methods for preparing ACNP formulations, and methods for treating a disease, such as cancer, in a subject with ACPN or a pharmaceutical formulation containing ACPN.
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Claims

1. A nanoparticle comprising a core, wherein the core comprises a polymer-XJ, wherein X is PEG', a linker, a PEG'-linker, or absent; J is a reactive group or is absent; and when J is a reactive group, a portion or all of J is optionally covalently bound to PEP-PEG" wherein PEP is a protease-sensitive protein sequence, and The polymer includes poly(lactic-co-glycolic acid) ("PLGA") having a ratio of lactic acid to glycolic acid ("LA:GA") of about 25:75, about 50:50, or about 75:25 (weight / weight).

2. The nanoparticle of claim 1 , wherein the ratio of lactic acid to glycolic acid ("LA:GA") is about 75:

25.

3. The nanoparticle of claim 1, wherein the molecular weight of the polymer is in the range of 10-100 kDA, 30 to 70 kDA, or 40-65 kDA.

4. The nanoparticle of claim 3, wherein the molecular weight of the polymer is in the range of 55-65 kDA, 42-62 kDA, or 45-55 kDA.

5. The nanoparticle of claim 1, wherein the nanoparticle is an antigen capture nanoparticle (ACNP). The nanoparticle of claim 1 , wherein the nanoparticle does not contain any antigen.

7. The nanoparticle of claim 1, wherein J is maleimide ("Mal").

8. The nanoparticle of claim 1, wherein the core of the nanoparticle comprises PLGA-X-maleimide 9. The nanoparticle of claim 1, wherein J is absent.

10. The nanoparticle of claim 1, wherein the core of the nanoparticle comprises PLGA or PLGA-X.

11. The nanoparticle of claim 1 , wherein the nanoparticle comprises a mixture of PLGA-XJ and PLGA-X in a mass ratio of 0.05:1 to 1:0.05, wherein X is PEG', a linker, a PEG'-linker, or absent, and a portion or all of J is optionally covalently bound to PEP-PEG", wherein PEP is a protease-sensitive protein sequence.

12. The nanoparticle of claim 11 , wherein the nanoparticle comprises a mixture of PLGA-X-maleimide and PLGA in a mass ratio of 0.05:1 to 1:0.05, wherein the maleimide is optionally covalently bound to PEP-PEG, wherein PEP is a protease-sensitive protein sequence.

13. The nanoparticle according to claim 12, wherein the mass ratio of PLGA-X-maleimide to PLGA is 1:

1.

14. The nanoparticle of claim 1, wherein PEP is capable of being cleaved by caspase, cathepsin, or MMP2.

15. The nanoparticle of claim 1, further comprising an adjuvant.

16. The nanoparticle of claim 15, wherein the adjuvant is a small molecule, a double-stranded RNA molecule, or a single-stranded DNA molecule.

17. The nanoparticle of claim 16, wherein the small molecule is imiquimod, resiquimod, or gademod.

18. The nanoparticle according to claim 16, wherein the double-stranded RNA molecule is poly (inosinic-cytidylic acid) ("poly-IC"), poly IC, Riboxxol 50. PolyIC, polyICLC, a complex between polyIC and poly(ethyleneimine) ("PEI"), or PEI mixed with a stabilizer.

19. The nanoparticle of claim 16, wherein the single-stranded DNA molecule is a CpG oligodeoxynucleotide (CpGODN).

20. The nanoparticle of claim 16, wherein the adjuvant is polyIC, PEI, or polyIC / PEI.

21. The nanoparticle of claim 1, wherein the nanoparticle is optionally lyophilized by a process comprising freeze drying or spray drying in the presence of a lyoprotectant.

22. The nanoparticle of claim 21, wherein the lyoprotectant is a buffer, a sugar molecule, a polymer, or a mixture thereof.

23. The nanoparticle of claim 22, wherein the lyoprotectant is HEPES-buffered saline ("HBS"), mannose, sucrose, trehalose, mannitol, poly(ethylene glycol) ("PEG"), poly(ethyleneimine) ("PEI"), poly(vinyl alcohol) ("PVA"), or a mixture thereof.

24. The nanoparticle of claim 23, wherein the lyoprotectant is HEPES-buffered saline ("HBS"), sucrose, PVA, or a mixture thereof.

25. A pharmaceutical preparation comprising the nanoparticles according to any one of claims 1 to 24 and a pharmaceutically acceptable carrier and / or excipient thereof.

26. The pharmaceutical formulation of claim 25, further comprising poly(vinyl alcohol) ("PVA") associated with the nanoparticles.

27. The pharmaceutical formulation of claim 26, wherein the mass ratio of the associated PVA to the core of the nanoparticle is 20-70% or 30-50%.

28. The pharmaceutical formulation of claim 25, wherein the formulation further comprises a buffer in the pH range of 7-8.

29. The pharmaceutical formulation of claim 28, wherein the buffer is HEPES buffer at pH 7.4 or HEPES buffered saline (HBS) at pH 7.

4.

30. A method for enhancing the effectiveness of cancer treatment in a subject in need thereof, comprising administering to the subject the nanoparticle of any one of claims 1-24 or the pharmaceutical composition of any one of claims 25-29.

31. The method of claim 30, wherein the composition is administered after the subject has been previously treated with an anti-cancer therapy.

32. The method of claim 31 , wherein the prior treatment is radiation.

33. The method of any one of claims 30-32, wherein the composition is used in combination with a second therapeutic agent.

34. The method of claim 33, wherein the second therapeutic agent is an immune checkpoint inhibitor.

35. The method of claim 34, wherein the immune checkpoint inhibitor is a PD-1 antibody.

36. The method of claim 30, wherein the cancer is brain cancer, non-small cell lung cancer, small cell lung cancer, esophageal cancer, gastric cancer, pancreatic cancer, colorectal cancer, renal cell carcinoma, bladder cancer, prostate cancer, breast cancer, non-Hodgkin lymphoma, Hodgkin lymphoma, anal cancer, head and neck cancer, or melanoma.