Genetically Modified NK-92 Cell Line for CD16-Mediated ADCC

The patent applies parameter changes by genetically modifying NK-92 cells to alter their receptor expression profile. Specifically, the cells are engineered to express CD16 Fc receptors through genetic transduction, transforming them from CD16-negative to CD16-positive status. This parameter change enables the cells to perform ADCC while preserving their inherent cytolytic activity, thus resolving the contradiction between maintaining cytolytic function and acquiring ADCC capability.

The patent creates a composite cell type by combining features of different cell populations. The modified NK-92 cells exhibit characteristics of both natural killer cells (cytolytic activity) and antibody-responsive cells (CD16 expression for ADCC). This composite nature allows the cells to function as dual-mode effector cells, simultaneously performing direct cyt lysis and antibody-dependent cytotoxicity, thereby resolving the functional limitation of the original cell line.

The patent applies segmentation by separating the modification process into distinct functional modules. The genetic modification uses modular vector systems where the CD16 coding sequence is inserted into specific genomic loci using defined protocols. This segmented approach to genetic engineering allows for controlled, reproducible modification while maintaining manageable complexity in the cell line development process.

The patent achieves universality by creating a broadly applicable modified cell line that can respond to multiple antibody types through CD16 expression. The genetically modified NK-92 cells serve multiple functions: they maintain their original cytolytic activity against various cancer cell lines and simultaneously acquire the ability to perform ADCC with different monoclonal antibodies. This multi-functionality reduces the need for developing separate cell lines for different therapeutic applications, thereby managing overall system complexity.