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Immunostimulatory biomaterials to boost tumor immunogenicity

期刊

BIOMATERIALS SCIENCE
卷 8, 期 20, 页码 5516-5537

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ROYAL SOC CHEMISTRY
DOI: 10.1039/d0bm01183e

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资金

  1. Ronald E. McNair Program at The University of Mississippi though US Department of Education [P217A170028]
  2. National Institute of General Medical Sciences of the National Institutes of Health [1P20GM130460-01A1]

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Cancer immunotherapy is exhibiting great promise as a new therapeutic modality for cancer treatment. However, immunotherapies are limited by the inability of some tumors to provoke an immune response. These tumors with a 'cold' immunological phenotype are characterized by low numbers of tumor-infiltrating lymphocytes, high numbers of immunosuppressive leukocytes (e.g.regulatory T cells, tumor-associated macrophages), and high production of immune-dampening signals (e.g.IL-10, TGF-beta, IDO-1). Strategies to boost the aptitude of tumors to initiate an immune response (i.e.boost tumor immunogenicity) will turn 'cold' tumors 'hot' and augment the anti-tumor efficacy of current immunotherapies. Approaches to boost tumor immunogenicity already show promise; however, multifaceted delivery and immunobiology challenges exist. For instance, systemic delivery of many immune-stimulating agents causes off-target toxicity and/or the development of autoimmunity, limiting the administrable dose below the threshold needed to achieve efficacy. Moreover, once administeredin vivo, molecules such as the nucleic acid-based agonists for many pattern recognition receptors are either rapidly cleared or degraded, and don't efficiently traffic to the intracellular compartments where the receptors are located. Thus, these nucleic acid-based drugs are ineffective without a delivery system. Biomaterials-based approaches aim to enhance current strategies to boost tumor immunogenicity, enable novel strategies, and spare dose-limiting toxicities. Here, we review recent progress to improve cancer immunotherapies by boosting immunogenicity within tumors using immunostimulatory biomaterials.

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