Glycan-Programmed T Cell Therapy with Sub-2 kDa Glycopeptides
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing immunization approaches targeting glycan epitopes like sTn or Tn antigens in cancer cells lack clinical efficacy due to low immunogenicity and T cell-independent IgM-driven immune responses, and classical immunization methods are challenging for glycan-based therapies.
Innovation Solution
Administering T cells isolated from a donor mammal treated with a composition of small glycopeptides, primarily derived from porcine gastrointestinal mucins, which include specific oligosaccharide structures, to treat cancer in a recipient mammal, potentially enhancing anti-tumor immunity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If classical immunization approaches targeting glycan epitopes are used, then immune recognition of tumor cells is enhanced, but the immune response is T cell-independent and driven by IgM, resulting in low clinical efficacy
Solution Approach 1:
The patent changes the molecular weight parameter of glycopeptides to less than 2 KDa, which fundamentally alters the immune response mechanism from T cell-independent IgM production to T cell-dependent responses, thereby achieving clinical efficacy while maintaining glycan target specificity
Solution Approach 2:
The patent segments large glycoproteins into small glycopeptide fragments less than 2 KDa, enabling these fragments to be processed and presented by MHC molecules to T cells, thus converting a B cell-only response into a T cell-dependent response that provides superior anti-tumor efficacy
2Reliability
If glycopeptides larger than 2 KDa are used, then more complete oligosaccharide structures are preserved, but MHC presentation to T cells is insufficient, resulting in poor T cell activation
Solution Approach 1:
The patent optimizes the molecular weight parameter of glycopeptides to be less than 2 KDa, which is the critical threshold that enables both MHC presentation capability and sufficient oligosaccharide structure integrity, achieving effective T cell activation
Solution Approach 2:
The patent creates simplified copies of complete glycan structures by using small glycopeptide fragments that contain the essential immunogenic epitopes, which are sufficient for MHC presentation and T cell recognition without requiring the full-size glycoprotein structure
Data Source
AI summary
Provided herein are methods treating cancer by administering to a recipient mammal reprogrammed T cells. The reprogrammed T cells of the disclosure is produced by a method comprising administering to the donor mammal an effective amount of a composition comprising a plurality of glycopeptides as described herein. Also provided are compositions comprising reprogrammed T cells and methods of producing reprogrammed T cells.