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

  • Article
  • Jan 10, 2022
  • #Biology
Luciano Santollani
@LSantollani
(Author)
Yash Agarwal
@yashagar7
(Author)
www.nature.com
Read on www.nature.com
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1 Mention
Anti-tumour inflammatory cytokines are highly toxic when administered systemically. Here, in multiple syngeneic mouse models, we show that the intratumoural injection of recombinant... Show More

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.

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Tony Kulesa @kulesatony · Jan 10, 2022
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Fantastic work from @yashagar7 @LSantollani and team! A cytokine engineering strategy to considerably increase tumor retention up to weeks, with minimal side effects.
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