NEO-201 Antibody Targeting Glycosylated gMDSCs for Immune Restoration
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Solution Overview
Problem
Current methods do not effectively detect and ablate myeloid-derived suppressor cells (MDSCs), which inhibit T cell function and contribute to various diseases, including cancer and infectious conditions.
Innovation Solution
Utilize the NEO-201 humanized IgG1 monoclonal antibody, which binds to glycosylated CEACAM5 and CEACAM6, to mediate ADCC and CDC against granulocyte-derived MDSCs, thereby depleting these cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used to detect and ablate MDSCs, then detection and ablation capability is maintained, but effectiveness against MDSCs is insufficient
Solution Approach 1:
The patent uses the NEO-201 antibody as an intermediary to detect and ablate MDSCs. The antibody specifically binds to glycosylated CEACAM5 and CEACAM6 proteins on the surface of MDSCs, enabling both detection (through binding) and ablation (through ADCC and CDC mechanisms). This intermediary approach overcomes the difficulty of directly detecting and eliminating these suppressor cells.
Solution Approach 2:
The invention exploits the presence of core-1 and extended core-1 O-glycans on CEACAM proteins as a distinguishing parameter between MDSCs and normal cells. By targeting this specific glycosylation pattern, the NEO-201 antibody achieves selective ablation of MDSCs while sparing normal cells that lack this glycosylation modification.
2Reliability
If NEO-201 antibody is used to ablate MDSCs, then MDSC depletion and immune restoration is achieved, but potential off-target effects on normal tissues must be considered
Solution Approach 1:
The NEO-201 antibody exhibits local quality by specifically targeting glycosylated CEACAM proteins that are locally present on MDSCs but absent or different on normal tissues. This localized specificity ensures that the antibody's ablation effect is confined to the intended target (MDSCs) while normal cells expressing non-glycosylated or differently glycosylated CEACAM variants remain unaffected.
Solution Approach 2:
The invention relies on the parameter change of glycosylation status to achieve selectivity. MDSCs express core-1 and extended core-1 O-glycans on their CEACAM proteins, whereas normal cells do not express this specific glycosylation pattern. The NEO-201 antibody is designed to recognize only this glycosylated form, thereby changing the selectivity parameter to favor MDSC ablation while minimizing off-target effects.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
NEO-201 effectively kills MDSCs, reversing tolerance and restoring innate immunity, enhancing the efficacy of other therapeutics by potentiating innate anti-tumor or anti-infectious responses, even in treatment-resistant subjects.
Implementation Method 1
NEO-201 has been demonstrated to be reactive against certain carcinomas, but not reactive against most normal tissues. NEO-201 effectively kills MDSCs, reversing tolerance and restoring innate immunity
Implementation Method 2
Utilize the NEO-201 humanized IgG1 monoclonal antibody, which binds to glycosylated CEACAM5 and CEACAM6, to mediate ADCC and CDC against granulocyte-derived MDSCs
Data Source
AI summary
NEO-201, an antibody that specifically binds to glycosylated peptides carrying core-1 and/or extended core-1 O-glycans comprised in CEACAM5 and CEAMCAM6 but not to aglycosylated CEACAM5 or aglycosylated CEAMCAM6 surprisingly has been shown to bind to and kill granulocyte myeloid derived suppressor cells (gMDSCs). gMDSCs are known to suppress innate immunity in different cancers and infectious diseases, among other conditions. Based thereon the use of NEO-201 alone or in combination for treating cancers and infectious diseases and other conditions wherein gMDSCs suppress innate immunity against the disease are provided. These methods optionally include detecting gMDSCs before, during or after NEO-201 treatment. Diagnostic methods, therapeutic methods, and combination therapies using NEO-201 optionally in combination with another agent in order to ablate gMDSCs and disease cells are also described.