Targeting specific sub-populations of cells remains a crucial challenge in both basic immunology research and immunotherapy. Existing technologies use a targeting component that binds specifically to one of the many potential identifying markers on the cell’s surface. However, sub-populations of immune cells relevant to tumors often have overlapping markers and therefore cannot be identified by a single marker, which is a limitation facing current approaches.
To overcome this issue, Dr. Holden is developing a two-component system that more effectively labels target cells by requiring the presence of two identifying markers. If both markers are present, only then will the system install a unique identifier on the cell surface for delivering labels, toxins, or other cargo. This modular system will be generalizable and provide a greater degree of control in accessing a variety of immune cell subsets, including those with immunosuppressive or cancer-killing activity.
After developing this two-component system, she will also seek to address the additional challenge of targeting T cells that can recognize and eliminate tumors. These tumor-specific killer T cells are critical for understanding anti-cancer immunity and guiding immunotherapy development, but are often rarer than other T cells, making them harder to identify. To that end, Dr. Holden will develop a targeting system using the same basic biochemical approach as the two-component system, providing a more sensitive and tunable technique to readily identify these important cells.
Projects and Grants
Precise Targeting of Distinct Immune Cell Subsets with an Enzymatic Approach
Broad Institute of MIT and Harvard | All Cancers | 2020 | Nir Hacohen, Ph.D.
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