Methods and compositions for identifying epitopes

The system of engineered APCs with exogenous nucleic acids and molecular reporters effectively identifies and recovers T cell-specific antigens, addressing the challenges of rare and complex antigen interactions, enhancing the discovery and recovery of relevant antigens.

AU2026205356A1Pending Publication Date: 2026-07-23THE BRIGHAM & WOMEN S HOSPITAL INC
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Patent Information

Authority / Receiving Office
AU · AU
Patent Type
Applications
Current Assignee / Owner
THE BRIGHAM & WOMEN S HOSPITAL INC
Filing Date
2026-07-07
Publication Date
2026-07-23

AI Technical Summary

Technical Problem

Identifying target antigens specific to T cells, such as cytotoxic T cells, is challenging due to the rarity and complexity of their interactions with antigen-presenting cells, leading to inefficient and biased discovery of antigens that may not be functionally displayed in vivo.

Method used

A system comprising antigen-presenting cells (APCs) engineered with exogenous nucleic acids encoding candidate antigens, a molecular reporter of Granzyme B activity, and an inhibitor of CAD-mediated DNA degradation, allowing for high-throughput detection and recovery of antigens recognized by cytotoxic lymphocytes.

Benefits of technology

Enables sensitive and robust identification of antigens recognized by cytotoxic T cells and NK cells, overcoming low throughput and bias in antigen discovery, and facilitating the recovery of presenting APCs and antigens driving immune responses.

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Abstract

Abstract Described herein, in one aspect, are antigen presenting cells (APCs) comprising an exogenous nucleic acid encoding one or more candidate antigens, wherein the one or more candidate antigens are expressed and presented with MHC class I or MC class II molecules; a molecular reporter of Granzyme B (GzB) activity; and c) an exogenous inhibitor of caspase-activated deoxyribonuclease (CAD)-mediated DNA degradation, a CAD knockout, or a caspase knockout (e.g., caspase 3 knockout). Described herein, in another aspect, is a system for detection of recognized antigen presentation by an antigen presenting cell to a cytotoxic lymphocyte or NK cell. Abstract 2018 / 22761 oM - cell Target ml Target cell cell cell Target Target Target SUBSTITUTE SHEET (RULE 26) cell cell cell Target Target cell cell 1 / 28 my Isolate recognized cell Library of target cells target cells and displaying different Add T cells from sample sequence antigens antigens of interest. CTLs deliver cytotoxic granules to target cells displaying cognate antigen FIG. 1 PCT / US2018 / 036663 20 26 20 53 56 07 J ul 2 02 6 2 0 2 6 2 0 5 3 5 6 0 7 J u l 2 0 2 6 2 0 1 8 / 2 2 7 6 1 o M a n d m y 1 / 2 8 m y L i b r a r y o f t a r g e t c e l l s d i s p l a y i n g d i f f e r e n tA d d T c e l l s f r o m s a m p l e of interest. CTLs deliver c y t o t o x i c g r a n u l e s t o t a r g e t c e l l s d i s p l a y i n g c o g n a t e a n t i g e n P C T / U S 2 0 1 8 / 0 3 6 6 6 3
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