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Intratumourally injected alum-tethered cytokines elicit potent and safer local and systemic anticancer immunity.

Authors :
Agarwal Y
Milling LE
Chang JYH
Santollani L
Sheen A
Lutz EA
Tabet A
Stinson J
Ni K
Rodrigues KA
Moyer TJ
Melo MB
Irvine DJ
Wittrup KD
Source :
Nature biomedical engineering [Nat Biomed Eng] 2022 Feb; Vol. 6 (2), pp. 129-143. Date of Electronic Publication: 2022 Jan 10.
Publication Year :
2022

Abstract

Anti-tumour inflammatory cytokines are highly toxic when administered systemically. Here, in multiple syngeneic mouse models, we show that the intratumoural injection of recombinantly expressed cytokines bound tightly to the common vaccine adjuvant aluminium hydroxide (alum) (via ligand exchange between hydroxyls on the surface of alum and phosphoserine residues tagged to the cytokine by an alum-binding peptide) leads to weeks-long retention of the cytokines in the tumours, with minimal side effects. Specifically, a single dose of alum-tethered interleukin-12 induced substantial interferon-γ-mediated T-cell and natural-killer-cell activities in murine melanoma tumours, increased tumour antigen accumulation in draining lymph nodes and elicited robust tumour-specific T-cell priming. Moreover, intratumoural injection of alum-anchored cytokines enhanced responses to checkpoint blockade, promoting cures in distinct poorly immunogenic syngeneic tumour models and eliciting control over metastases and distant untreated lesions. Intratumoural treatment with alum-anchored cytokines represents a safer and tumour-agnostic strategy to improving local and systemic anticancer immunity.<br /> (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Details

Language :
English
ISSN :
2157-846X
Volume :
6
Issue :
2
Database :
MEDLINE
Journal :
Nature biomedical engineering
Publication Type :
Academic Journal
Accession number :
35013574
Full Text :
https://doi.org/10.1038/s41551-021-00831-9