Engineering nanoparticles to locally activate T cells in the tumor microenvironment

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Science Immunology  12 Jul 2019:
Vol. 4, Issue 37, eaau6584
DOI: 10.1126/sciimmunol.aau6584

Targeted tumor immunotherapy

Although immunotherapy has transformed the cancer therapeutics landscape, a number of problems remain to be solved, from improving efficacy to limiting side effects. Here, Wang et al. have attempted to do this by engineering nanoparticles that can be specifically activated within tumors by conjugating antibodies against programmed death ligand 1 (PDL1) with matrix metalloproteinase protein 2 (MMP-2)–sensitive nanoparticles that carry a photosensitizer. MMP-2 is highly expressed in tumors, and delivery of the nanoparticle to tumors elicits release of the antibody from the nanoparticle. When used in conjunction with localized near-infrared radiation that activates the photosensitizer to produce reactive oxygen species, Wang et al. show that these nanoparticles outperform systemic anti-PDL1 in limiting growth and metastasis of murine tumors.

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