Harnessing chitosan and poly-(gamma-glutamic acid)-based biomaterials towards cancer immunotherapy

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Raquel GFlonçalves (Author) Other; Maria José Oliveira (Author) Other; Mário A. Barbosa (Author) Other; Beatriz Lima (Author) Other; Flávia Castro (Author) Other

Journal

The Journal is awaiting validation by the Administrative Services.

Title: MATERIALS ADVANCES

Vol. 15

ISSN: 2633-5409

Indexing

ISI Web of Knowledge - 8 Citations

Scopus - 8 Citations

Other information

Authenticus ID: P-00X-801

DOI: 10.1016/j.mtadv.2022.100252

Abstract (EN): Cancer-related immunosuppression is one of the most challenging aspects of cancer therapy, being one of the principal causes of disease relapse. Most recent immunotherapeutic strategies have been at the forefront of therapies to overcome this problem through targeting T cell-related pathways. Notwithstanding their remarkable clinical success, current immunotherapies have still benefited a small percentage of patients. As such, considering solid tumors are virtually infiltrated by a high proportion of innate immune cells, frequently mentioned as masters of immunosuppression, targeting these cells may offer a durable immune response. Thus, finding new strategies to reprogram the function of innate immune system in the tumor microenvironment is still an unmet clinical need. Biomaterials-based immunomodulatory therapies have been increasingly explored to achieve better cancer treatments. In particular, chitosan (Ch), a polysaccharide derived from the deacetylation of chitin, as well as poly-gamma-glutamic acid (gamma-PGA), a polymer bacterially synthetized, that can spontaneously self-assemble by electrostatic interactions in different structures, have been preclinically explored for their immunomodulatory properties. Ch and gamma-PGA have been found to activate Toll-like receptors, and trigger common pro-inflammatory immune pathways, such as Nuclear factor kappa B (NF-kappa B) and Mitogen-activated protein kinase (MAPK). Other pathways and receptors, such as the Retinoic Acid Orphan Receptor gamma t (ROR gamma t), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), or the inflammasome have also been shown to be differentially activated by either polymer. Hence the prospective application of Ch/gamma-PGA formulations in cancer therapy, in an effort to synergize their effects to heighten the therapeutic response via innate immunity, could constitute a novel immunotherapeutic strategy. This review highlights how Ch and gamma-PGA can efficiently reprogram innate immune cells in tumors, and ultimately initiate activation of T cell immunity against advanced cancers. Moreover, the therapeutic potential of Ch/gamma-PGA-based biomaterials as adjuvants of conventional cancer therapies and as diagnostic tools is discussed. (C) 2022 Published by Elsevier Ltd.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14