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Updated: Jan 19, 2026
Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies
Published on: May 22, 2020
Anti-myeloma activity and molecular logic operation by Natural Killer cells in microfluidic droplets
Saheli Sarkar1, Seamus McKenney1, Pooja Sabhachandani1
1Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA, 02115.
Abstract:
Immune-targeted therapies that activate effector lymphocytes such as Natural Killer (NK) cells are currently being investigated for the treatment of Multiple myeloma (MM), the second most common form of hematological cancer. However, individual NK cells are highly heterogeneous in their cytolytic potential, making it difficult to detect, quantify and correlate the outcome of dynamic effector-target cell interactions at single cell resolution. Here, we present a microfluidic bioassay platform capable of activity-based screening of cellular and molecular immunotherapies. We identified distinct functional signatures associated with NK-MM cell interaction. The addition of immunomodulatory drug lenalidomide altered responses of NK-susceptible MM cells but not that of NK-tolerant MM cells. Antitumor cytotoxicity was significantly increased by the blockade of PD1/PDL1 axis as well as the clinically relevant cell line NK92, which were used to construct molecular logic functions (AND and NOT gates). A predictive agent-based mathematical model was developed to simulate progressive disease states and drug efficacy. The findings of the current study validate the applicability of this microfluidic cytotoxicity assay for immunotherapy screening, biocomputation and for future employment in detection of patient-specific cell response for precision medicine.
Insights
A new microfluidic platform enables precise measurement of Natural Killer (NK) cell immunotherapy effectiveness against Multiple myeloma (MM). This technology aids in developing personalized cancer treatments by analyzing single-cell responses.
Area of Science:
- Immunology
- Biotechnology
- Oncology
Background:
- Multiple myeloma (MM) is a hematological cancer with limited treatment options.
- Natural Killer (NK) cells show potential for immune-targeted therapies against MM.
- NK cell heterogeneity complicates the assessment of immunotherapy efficacy at the single-cell level.
Purpose of the Study:
- To develop and validate a microfluidic bioassay for high-resolution screening of immunotherapies.
- To characterize functional interactions between NK cells and MM cells.
- To explore the potential for precision medicine in MM treatment.
Main Methods:
- Development of a microfluidic bioassay platform for activity-based screening.
- Analysis of NK-MM cell interactions and functional signatures.
- Assessment of drug responses (lenalidomide) and immunotherapy targets (PD1/PDL1 blockade, NK92 cells).
- Construction of molecular logic gates and development of a predictive mathematical model.
Main Results:
- Distinct functional signatures of NK-MM cell interactions were identified.
- Lenalidomide modulated responses in NK-susceptible MM cells.
- PD1/PDL1 blockade and NK92 cells significantly enhanced antitumor cytotoxicity.
- The platform successfully constructed molecular logic functions.
Conclusions:
- The microfluidic cytotoxicity assay is effective for screening immunotherapies and biocomputation.
- The platform can be used for patient-specific cell response detection for precision medicine in MM.
- This technology advances the development of targeted cancer therapies.
