Paracrine release of IL-2 and anti-CTLA-4 enhances the ability of artificial polymer antigen-presenting cells to expand antigen-specific T cells and inhibit tumor growth in a mouse model

Cancer Immunology, Immunotherapy : CII
Lei ZhangChuanlai Shen

Abstract

Accumulating evidence indicates that bead-based artificial antigen-presenting cells (aAPCs) are a powerful tool to induce antigen-specific T cell responses in vitro and in vivo. To date, most conventional aAPCs have been generated by coupling an antigen signal (signal 1) and one or two costimulatory signals, such as anti-CD28 with anti-LFA1 or anti-4-1BB (signal 2), onto the surfaces of cell-sized or nanoscale magnetic beads or polyester latex beads. The development of a biodegradable scaffold and the combined use of multiple costimulatory signals as well as third signals for putative clinical applications is the next step in the development of this technology. Here, a novel biodegradable aAPC platform for active immunotherapy was developed by co-encapsulating IL-2 and anti-CTLA-4 inside cell-sized polylactic-co-glycolic acid microparticles (PLGA-MPs) while co-coupling an H-2Kb/TRP2-Ig dimer and anti-CD28 onto the surface. Cytokines (activating signal) and antibodies (anti-inhibition signal) were efficiently co-encapsulated in PLGA-MP-based aAPCs and co-released without interfering with each other. The targeted, sustained co-release of IL-2 and anti-CTLA-4 achieved markedly enhanced, synergistic effects in activating and expand...Continue Reading

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Citations

Sep 19, 2020·Cells·Ernesto BockampDetlef Schuppan
Jun 12, 2020·Acta Biomaterialia·Kelly R RhodesJordan J Green
Mar 12, 2018·Molecular Immunology·Kelly R Rhodes, Jordan J Green
Apr 29, 2021·Macromolecular Bioscience·Ai Lin ChinRong Tong
Jul 24, 2021·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Christine E BooneNicole F Steinmetz
Sep 12, 2020·Chemical Reviews·Wen-Hao Li, Yan-Mei Li

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