Yash Agarwal

Conference 2023 Live Talk

Talk title

A materials-based approach for localized delivery of cancer immunotherapy

Authors and Affiliations

Yash Agarwal 1,2, Lauren E. Milling1,2, Jason Y. H. Chang 2,3, Luciano Santollani2,4, Allison Sheen1,2, Emi A. Lutz 1,2, Anthony Tabet2,4, Jordan Stinson1,2, Kaiyuan Ni2
, Kristen A. Rodrigues 2,3,5,6, Tyson J. Moyer2,3, Mariane B. Melo 2,3, Darrell J. Irvine 1,2,3,6,7,8  and K. Dane Wittrup 1,2,4

1. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
2. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
3.Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
4. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
5. Harvard-MIT Health Sciences and Technology Program, Institute of Medical Engineering and Science, Massachusetts Institute of Technology,
Cambridge, MA, USA.
6. Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA, USA.
7. Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. 8Howard Hughes Medical Institute, Chevy Chase, MD, USA.

Abstract

Background

Anti-tumour inflammatory cytokines are highly toxic when administered systemically.

Methods

N/A

Results

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.

Conclusions

Intratumoural treatment with alum-anchored cytokines represents a safer and tumour-agnostic strategy to improving local and systemic anticancer immunity.