Related Experiment Video
Updated: Jul 19, 2025
Fabrication of Anisotropic Polymeric Artificial Antigen Presenting Cells for CD8+ T Cell Activation
Published on: October 12, 2018
Polymer Micropatches as Natural Killer Cell Engagers for Tumor Therapy
Supriya Prakash1,2, Ninad Kumbhojkar1,2, Andrew Lu1
1Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Allston, Massachusetts 02134, United States.
Abstract:
Natural killer (NK) cell therapies have emerged as a potential therapeutic approach to various cancers. Their efficacy, however, is limited by their low persistence and anergy. Current approaches to sustain NK cell persistence in vivo include genetic modification, activation via pretreatment, or coadministration of supporting cytokines or antibodies. Such supporting therapies exhibit limited efficacy in vivo, in part due to the reversal of their effect within the immunosuppressive tumor microenvironment and off-target toxicity. Here, we report a material-based approach to address this challenge. Specifically, we describe the use of polymeric micropatches as a platform for sustained, targeted activation of NK cells, an approach referred to as microparticles as cell engagers (MACE). Poly(lactide-co-glycolic) acid (PLGA) micropatches, 4-8 μm in diameter and surface-modified with NK cell receptor targeting antibodies, exhibited strong adhesion to NK cells and induced their activation without the need of coadministered cytokines. The activation induced by MACE was greater than that induced by nanoparticles, attesting to the crucial role of MACE geometry in the activation of NK cells. MACE-bound NK cells remained viable and exhibited trans-endothelial migration and antitumor activity in vitro. MACE-bound NK cells activated T cells, macrophages, and dendritic cells in vitro. Adoptive transfer of NK-MACE also demonstrated superior antitumor efficacy in a mouse melanoma lung metastasis model compared to unmodified NK cells. Overall, MACE offers a simple, scalable, and effective way of activating NK cells and represents an attractive platform to improve the efficacy of NK cell therapy.
Insights
Polymeric micropatches, termed microparticles as cell engagers (MACE), effectively activate natural killer (NK) cells. This material-based approach enhances NK cell persistence and antitumor activity, offering a promising strategy for cancer immunotherapy.
Area of Science:
- Biomaterials Science
- Immunology
- Cancer Therapy
Background:
- Natural killer (NK) cell therapy shows promise for cancer treatment but is hindered by poor *in vivo* persistence and anergy.
- Existing methods to enhance NK cell function, such as genetic modification or cytokine support, face limitations due to the tumor microenvironment and off-target effects.
Purpose of the Study:
- To develop a material-based strategy for sustained and targeted activation of NK cells.
- To investigate the efficacy of polymeric micropatches, termed microparticles as cell engagers (MACE), as a novel platform for enhancing NK cell-based cancer immunotherapy.
Main Methods:
- Fabrication of poly(lactide-co-glycolic) acid (PLGA) micropatches (4-8 μm) surface-modified with NK cell receptor targeting antibodies.
- Assessment of MACE adhesion, NK cell activation, viability, trans-endothelial migration, and *in vitro* cross-talk with other immune cells.
- Evaluation of the *in vivo* antitumor efficacy of NK-MACE in a murine melanoma lung metastasis model.
Main Results:
- MACE demonstrated strong adhesion to NK cells, inducing potent activation without exogenous cytokines, surpassing nanoparticle-based activation.
- MACE-bound NK cells maintained viability, exhibited trans-endothelial migration, and showed *in vitro* antitumor activity and immune cell activation.
- Adoptive transfer of NK-MACE significantly improved antitumor efficacy in a preclinical lung metastasis model compared to unmodified NK cells.
Conclusions:
- Microparticles as cell engagers (MACE) provide a scalable and effective material-based platform for sustained NK cell activation.
- MACE represents a promising strategy to overcome NK cell limitations and enhance the efficacy of NK cell-based cancer immunotherapy.
More Related Videos
Related Concept Videos
01:27Tumor Immunotherapy
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
01:25Immune Surveillance by NK Cells and Phagocytes
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
01:28Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...