Engineered Cells with Surface Glycan Moieties for Cancer Targeting
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Solution Overview
Problem
Current cancer immunotherapy methods, such as adoptive cell therapy and checkpoint blockade therapy, face limitations in the migratory potential and effectiveness of T-cells and natural killer (NK) cells, particularly due to the lack of sufficient active NK cells and the limited targeting capabilities of dendritic cells, which restrict their application in treating cancer.
Innovation Solution
Engineered cells with chemical or biological moieties covalently bound to their surface glycans, such as antibodies like Trastuzumab, are developed to enhance their migratory abilities and targeting specificity, allowing them to effectively bind to cancer cells and block immune checkpoints, thereby improving cancer treatment outcomes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If NK-92 cells are used to generate larger numbers of cytotoxic NK cells, then the quantity of NK cells is improved, but the targeting capability is worsened due to lack of Fc receptors for ADCC effects
Solution Approach 1:
The NK-92MI cell is engineered to perform multiple functions: it retains the cytotoxic capabilities of NK-92 cells while simultaneously acquiring FcγRIIIA (CD16) expression to enable ADCC effects. This multi-functional design allows the cell to both kill target cells directly through cytotoxicity and indirectly through antibody-dependent mechanisms, thereby resolving the contradiction between quantity and targeting capability.
Solution Approach 2:
The patent introduces FcγRIIIA (CD16) as an intermediary component on the NK-92MI cell surface that mediates the interaction between antibodies and target cells. This intermediary enables the cell to bind to antibody-coated target cells through ADCC, providing the missing targeting capability while preserving the high cell numbers generated from NK-92 expansion.
2Reliability
If dendritic cells are administered for cancer immunotherapy, then the immune response is improved, but the migratory ability is worsened as only a small portion reaches secondary lymphatic organs
Solution Approach 1:
The patent modifies the surface properties of dendritic cells by engineering them to express specific surface markers and molecules that enhance their migratory capacity. This parameter change in cell surface characteristics enables a larger proportion of administered DCs to successfully migrate to secondary lymphatic organs, thereby improving both migratory speed and the reliability of the immune response.
3Reliability
If T-cells are infused for adoptive cell therapy, then the cancer fighting property is improved, but the migratory potential is worsened limiting their effectiveness
Solution Approach 1:
The patent engineers T-cells with modified surface parameters, including expression of specific homing receptors and adhesion molecules, to enhance their migratory potential. These parameter changes enable the T-cells to more effectively navigate to tumor sites while preserving their cancer-killing capabilities, thus resolving the contradiction between migratory potential and cancer fighting property.
Data Source
AI summary
Provided herein are engineered cells, comprising: a chemical or biological moiety covalently bound to a cell surface glycan, wherein the chemical or biological moiety is selected from the group consisting of small molecule, polynucleotide, polypeptide, and antibody. Also provided are compositions comprising these engineered cells and methods of making and using the same.