Issue 16, 2022

Spatial delivery of immune cues to lymph nodes to define therapeutic outcomes in cancer vaccination

Abstract

Recently approved cancer immunotherapies – including CAR-T cells and cancer vaccination, – show great promise. However, these technologies are hindered by the complexity and cost of isolating and engineering patient cells ex vivo. Lymph nodes (LNs) are key tissues that integrate immune signals to coordinate adaptive immunity. Directly controlling the signals and local environment in LNs could enable potent and safe immunotherapies without cell isolation, engineering, and reinfusion. Here we employ intra-LN (i.LN.) injection of immune signal-loaded biomaterial depots to directly control cancer vaccine deposition, revealing how the combination and geographic distribution of signals in and between LNs impact anti-tumor response. We show in healthy and diseased mice that relative proximity of antigen and adjuvant in LNs – and to tumors – defines unique local and systemic characteristics of innate and adaptive response. These factors ultimately control survival in mouse models of lymphoma and melanoma. Of note, with appropriate geographic signal distributions, a single i.LN. vaccine treatment confers near-complete survival to tumor challenge and re-challenge 100 days later, without additional treatments. These data inform design criteria for immunotherapies that leverage biomaterials for loco-regional LN therapy to generate responses that are systemic and specific, without systemically exposing patients to potent or immunotoxic drugs.

Graphical abstract: Spatial delivery of immune cues to lymph nodes to define therapeutic outcomes in cancer vaccination

Supplementary files

Article information

Article type
Paper
Submitted
18 Mac 2022
Accepted
13 Mei 2022
First published
28 Jun 2022

Biomater. Sci., 2022,10, 4612-4626

Author version available

Spatial delivery of immune cues to lymph nodes to define therapeutic outcomes in cancer vaccination

J. I. Andorko, S. J. Tsai, J. M. Gammon, S. T. Carey, X. Zeng, E. A. Gosselin, C. Edwards, S. A. Shah, K. L. Hess and C. M. Jewell, Biomater. Sci., 2022, 10, 4612 DOI: 10.1039/D2BM00403H

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