GM3-OMPC Nanoparticles for MDSC Reduction in Cancer
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Solution Overview
Problem
Current nano-particulate systems targeting Myeloid-derived suppressor cells (MDSCs) in cancer treatment are limited by size restrictions, lack of effect on MDSCs, and are primarily tested in murine models, with only a few strategies showing promise, and none effectively decrease MDSC levels in humans.
Innovation Solution
A novel nano-particulate immunomodulator composed of hydrophobic conjugates of Neisseria meningitidis outer membrane protein complex (OMPC) and GM3 ganglioside, with specific size, surface charge, and morphology, administered subcutaneously to decrease MDSC levels and enhance T cell response in cancer patients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional nano-particulate systems are used to target MDSCs, then the treatment approach is established, but the systems fail to effectively decrease MDSC levels in humans due to size restrictions and lack of direct effect on MDSCs
Solution Approach 1:
The patent changes the size parameter of nanoparticles to a specific range (20-200 nm) that enables effective drainage to lymph nodes and direct interaction with MDSCs in human patients, overcoming the size restrictions of conventional systems. This parameter optimization allows the nanoparticles to achieve both lymph node targeting and direct MDSC suppression efficacy in humans.
Solution Approach 2:
The patent uses nanoparticles as intermediary carriers that deliver immunomodulatory agents directly to MDSCs in the lymph nodes, enabling the treatment effect without requiring the nanoparticles themselves to directly kill MDSCs. This intermediary approach allows conventional immunomodulators to be delivered precisely to the target cells, achieving effectiveness that neither component could achieve alone.
2Force
If nano-particles with diameters in the range of 500-2000 nm are used, then they are preferentially captured at the injection site and moved to lymph nodes, but they do not effectively interact with resident cells including MDSCs
Solution Approach 1:
The patent optimizes the nanoparticle size parameter to 20-200 nm, which is smaller than conventional systems (500-2000 nm). This size reduction enables the nanoparticles to pass through lymphatic vessels more efficiently and directly interact with resident cells including MDSCs in the lymph nodes, while still maintaining effective drainage from the injection site.
3Ease of manufacture
If existing nano-particle strategies are used, then they serve as carrier systems, but they lack per se effect on MDSCs requiring additional therapeutic agents
Solution Approach 1:
The patent designs nanoparticles with multi-functionality: they serve as carrier systems for delivering immunomodulatory agents to MDSCs, while simultaneously possessing inherent properties (size, surface characteristics) that enable direct interaction with and suppression of MDSCs. This dual functionality eliminates the need for separate therapeutic agents, simplifying the overall treatment approach.
4Reliability
If immunomodulators are designed to restore T cell response, then the antitumor immune response is enhanced, but MDSC-mediated suppression must be overcome first
Solution Approach 1:
The patent applies preliminary action by first targeting and suppressing MDSCs in the lymph nodes before restoring T cell response. The nanoparticles deliver immunomodulatory agents that reduce MDSC suppressive function, creating a favorable immune environment that then allows T cells to effectively respond to tumor antigens. This sequential approach ensures that suppression is removed before restoration can occur.
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
The immunomodulator significantly decreases granulocytic and monocytic MDSCs, restoring T cell response and improving patient survival by reducing MDSC-mediated immune suppression in cancer patients.
Implementation Method 1
nanoparticles formed by hydrophobic conjugation of the outer membrane protein complex (OMPC) of the N. meningitidis bacterium to GM3 ganglioside
Data Source
AI summary
The present invention describes a pharmaceutical composition whose active ingredient includes conjugates of membrane vesicles of Neisseria meningitidis and the GM3 ganglioside in a conjugation ratio in excess of proteins, has particular characteristics of size, surface charge and a morphology associated with nano-particulate systems that give it advantageous properties as an immunomodulator, because it induces a convenient and significant reduction of myeloid-derived suppressor cells that has an impact on the response of lymphocytes and on the survival of patients with tumors. The invention further discloses the use of the pharmaceutical composition disclosed in the treatment of cancer, particularly those cancers where the myeloid-derived suppressor cells (MDSCs) are high; as well as a method of treatment with said composition in cancer patients and a method to select those who will receive said treatment.