Monday, August 14, 2023

PLGA-Rhodamine from PolySciTech used in development of immunotherapy treatment of cancer

 


Macrophages are the bodies natural defense mechanism against disease and infection. These cells can be modified utilizing micropatches which attach to them and encourage them to attach cancer cells. Researchers at Harvard University utilized fluorescent PLGA-Rhodamine (AV011) from PolySciTech division of Akina, Inc. (www.polyscitech.com) as part of their development of macrophage cell engagers to target macrophages against cancer. This research holds promise to provide improved therapies against cancer in the future. Read more: Prakash, Supriya, Ninad Kumbhojkar, Andrew Lu, Neha Kapate, Vineeth Chandran Suja, Kyung Soo Park, Lily Li-Wen Wang, and Samir Mitragotri. "Polymer Micropatches as Natural Killer Cell Engagers for Tumor Therapy." ACS nano (2023). https://pubs.acs.org/doi/abs/10.1021/acsnano.3c03980

“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. KEYWORDS: NK cell NK engager NK cell activation cross-linking microparticle adoptive cell transfer lung metastasis”

No comments: