Back to Our Technologies

A Method of Using Biomarkers to Determine Whether Immunotherapy Will Be More Effective Using T-cells or Natural Killer (NK) Cells

Systematic characterisation of molecular features of human tumor cells that determine their sensitivity to allogeneic NK cells

  • Diagnostics

Project Overview

  • Natural Killer (NK) cells are viewed as a safe and effective form of immunotherapy.
  • Studies looking into the mechanisms regulating cell responses in NK cells have not been generalizable to a broad range of human cancers.
  • A new technology developed at Dana-Farber systematically characterizes the molecular features of human tumor cells that determine their sensitivity to allogeneic NK cells.
  • Dana‑Farber is looking for collaboration partners to develop companion diagnostics for NK cell therapy.

Technology

Natural Killer (NK) cells are viewed as a safe and effective form of immunotherapy. More research is needed to investigate which molecules/pathway in tumor cells determine the degree of the tumor’s responsiveness to the cytotoxic activity of NK cells. However, studies looking into the mechanisms regulating cell responses in NK cells have been primarily conducted on leukemic cell lines (K562) which are highly NK cell‑sensitive. This has led to a lack of generalizability of findings to a broader range of human cancers.

This technology aims to systematically characterize the molecular features of human tumor cells that determine their sensitivity to allogeneic NK cells. This involves using high-throughput platforms such as the PRISM (Profiling Relative Inhibition Simultaneously in Mixtures) approach and CRISPR/Cas9-based gene editing to analyze a wide array of solid tumor cell lines. The identified biomarkers can determine whether NK cell-based or T‑cell based immunotherapy will provide better outcomes to certain patients with specific biomarkers.

This new technology claims the methods of identifying biomarkers to select patients who are more likely to respond well to either NK cell-based or T cell-based therapies in a variety of different hematological cancers and solid tumors. The study discovered that B7-H6, various genes involved in antigen presentation machinery (including HLA-E), genes implicated in the regulation of death receptor signaling, as well as diverse epigenetic and post-translational regulators (including genes in the N-glycan biosynthesis pathway, amino sugar metabolism) are major determinants for response to NK cell cytotoxicity.

By providing a method for selecting patients most likely to benefit from specific immunotherapies, the technology could improve treatment outcomes and reduce unnecessary side effects. Also, the profiling of cell‑surface proteins and combining immunotherapy with other agents could contribute to the development of more effective cancer treatments. 

Further Details:

Sheffer, M., et al. (2021). Genome-scale screens identify factors regulating tumor cell responses to natural killer cells. Nature Genetics, 53(8), 1196–1206. https://doi.org/10.1038/s41588-021-00889-w

Team Members: Constantine S. Mitsiades, MD, PhD

Applications

  • Companion Diagnostic
  • Biomarker for treatment

Opportunities

Dana‑Farber Cancer Institute is looking for collaboration partners to develop companion diagnostics for NK cell therapy

Get in touch

Team Members