2024-03-18 ハーバード大学
<関連情報>
- https://seas.harvard.edu/news/2024/03/empty-backpacks-activate-immune-system-against-cancer
- https://www.nature.com/articles/s41551-024-01180-z
接着性ポリマー微小粒子を持つ好中球を、薬剤を使わないがん免疫療法として利用できる Neutrophils bearing adhesive polymer micropatches as a drug-free cancer immunotherapy
Ninad Kumbhojkar,Supriya Prakash,Tatsuya Fukuta,Kwasi Adu-Berchie,Neha Kapate,Rocky An,Solomina Darko,Vineeth Chandran Suja,Kyung Soo Park,Alexander P. Gottlieb,Michael Griffith Bibbey,Malini Mukherji,Lily Li-Wen Wang,David J. Mooney & Samir Mitragotri
Nature Biomedical Engineering Published:29 February 2024
DOI:https://doi.org/10.1038/s41551-024-01180-z
Abstract
Tumour-associated neutrophils can exert antitumour effects but can also assume a pro-tumoural phenotype in the immunosuppressive tumour microenvironment. Here we show that neutrophils can be polarized towards the antitumour phenotype by discoidal polymer micrometric ‘patches’ that adhere to the neutrophils’ surfaces without being internalized. Intravenously administered micropatch-loaded neutrophils accumulated in the spleen and in tumour-draining lymph nodes, and activated splenic natural killer cells and T cells, increasing the accumulation of dendritic cells and natural killer cells. In mice bearing subcutaneous B16F10 tumours or orthotopic 4T1 tumours, intravenous injection of the micropatch-loaded neutrophils led to robust systemic immune responses, a reduction in tumour burden and improvements in survival rates. Micropatch-activated neutrophils combined with the checkpoint inhibitor anti-cytotoxic T-lymphocyte-associated protein 4 resulted in strong inhibition of the growth of B16F10 tumours, and in complete tumour regression in one-third of the treated mice. Micropatch-loaded neutrophils could provide a potent, scalable and drug-free approach for neutrophil-based cancer immunotherapy.
