Conjugated virus-like particles and uses thereof as anti-tumor immune redirectors
Inventors
WANG, Joshua Weiyuan • INGAVAT, Nattha • Matsui, Ken
Assignees
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Publication Number
US-12528839-B2
Publication Date
2026-01-20
Expiration Date
Abstract
Disclosed is a new class of conjugated virus-like particles (VLPs). These conjugated VLPs bind a wide variety of tumors and comprise epitopes recognized by a prior T cell immune response already existing in a host. These epitopes are derived from pathogens or previous vaccinations (such as early childhood vaccines). This provokes the body's pre-existing cytotoxic immunity obtained through previous infection or previous childhood vaccination to be redirected to the tumor cells for the elimination of cancer, and form long-term anti-tumor immunity. The described conjugated VLPs are useful for tailoring a broad range of tumors towards a response from existing immunity circumventing the need to identify tumor antigens or generate tumor-specific immune responses. Importantly, the compositions and methods described herein broadens opportunities for treatment for all cancer types in subjects who previously had un-targetable cancers due to various technological and biological limitations of currently available immuno-therapeutic drugs.
Core Innovation
The invention provides a method of treating cancer by administering to a subject a pharmaceutically effective amount of a virus-like particle (VLP). The VLP includes at least one virus capsid protein and a fusion protein built as a single peptide in order from amino terminus to carboxy terminus, and the fusion protein includes at least one protease cleavage peptide sequence attached to at least one recall protein comprising at least one epitope.
The protease cleavage peptide sequence is recognized by tumor microenvironment proteases selected from cathepsins, kallikreins, serine proteases, caspases, matrix metalloproteinases, and ADAMs. The fusion protein is 45 amino acids or less in length, and the recall protein comprises at least one human T cell epitope from 8 to 17 amino acids in length.
The VLP is also configured so that the at least one virus capsid protein exhibits tropism for a specific type of tissue. The disclosed approach uses recall epitopes derived from prior pathogen exposure or childhood or adult vaccination and is presented as broadly applicable across multiple cancer types with anti-tumor immune redirection and tumor control outcomes.
Claims Coverage
The partial claims include two independent claims. Across these independent claims, the inventive coverage is centered on a single-peptide VLP architecture with a virus capsid protein and a protease-cleavable recall fusion protein, tumor microenvironment protease recognition, specified length constraints for the fusion protein and epitope, and capsid tropism for a specific tissue type, with cancer type selection for the treatment method claim.
Protease-cleavable recall fusion protein as a single-peptide VLP
A VLP in order from amino terminus to carboxy terminus as a single peptide comprising at least one virus capsid protein and a fusion protein comprising at least one protease cleavage peptide sequence attached to at least one recall protein comprising at least one epitope.
Tumor microenvironment protease recognition of the cleavage peptide
The at least one protease cleavage peptide sequence is recognized by one or more tumor microenvironment protease selected from cathepsins, kallikreins, serine proteases, caspases, matrix metalloproteinases, and ADAMs.
Length constraints on fusion protein and recall epitope
The fusion protein is 45 amino acids or less in length, and the at least one recall protein comprises at least one epitope from 8 to 17 amino acids in length, wherein the at least one epitope is at least one human T cell epitope.
Capsid tropism for tissue targeting
The at least one capsid protein exhibits tropism for a specific type of tissue.
Cancer type selection for treating with the VLP
The cancer is selected from the group consisting of lung, oral, cervical, epithelial, ovary, breast, colon, and prostate.
The independent claim set covers a VLP architecture in which a virus capsid protein and a protease-cleavable recall fusion protein are arranged as a single peptide, where tumor microenvironment proteases recognize the cleavage sequence and the recall component provides a human T cell epitope within specified length ranges; one independent claim further requires capsid tropism for a specific tissue type, and the method claim limits the cancer to a defined set.
Stated Advantages
Redirects cytotoxic CD8 T-cell immunity against the tumor by presenting recall T-cell epitopes in the tumor microenvironment.
Generates durable anti-tumor immunity without needing individualized tumor antigen identification.
Documented Applications
Treatment of cancer in a subject, where the cancer is selected from lung, oral, cervical, epithelial, ovary, breast, colon, and prostate.
Treatment of cancers for which the VLP capsid protein exhibits tropism for a specific type of tissue.
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