2. Academic Validation
  3. Local delivery of cell surface-targeted immunocytokines programs systemic anti-tumor immunity

Local delivery of cell surface-targeted immunocytokines programs systemic anti-tumor immunity

  • bioRxiv. 2024 Jan 3:2024.01.03.573641. doi: 10.1101/2024.01.03.573641.
Luciano Santollani 1 2,  Yiming J Zhang 2 3,  Laura Maiorino 2 4,  Joseph R Palmeri 1 2,  Jordan A Stinson 2 3,  Lauren R Duhamel 2 3,  Kashif Qureshi 2,  Jack R Suggs 1 2,  Owen T Porth 2 3,  William Pinney 3rd 2 3,  Riyam Al Msari 2 3,  K Dane Wittrup 1 2 3,  Darrell J Irvine 2 3 5 4 6
Affiliations

Affiliations

  • 1 Department of Chemical Engineering, Massachusetts Institute of Technology; Cambridge, MA, USA.
  • 2 Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge; MA, USA.
  • 3 Department of Biological Engineering, Massachusetts Institute of Technology; Cambridge, MA, USA.
  • 4 Howard Hughes Medical Institute; Chevy Chase, MD, USA.
  • 5 Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University; Cambridge, MA, USA.
  • 6 Department of Materials Science and Engineering; Massachusetts Institute of Technology, Cambridge, MA, USA.
PMID: 38260254 DOI: 10.1101/2024.01.03.573641
Abstract

Cytokine therapies are potent immunotherapy agents but exhibit severe dose-limiting toxicities. One strategy to overcome this involves engineering cytokines for intratumoral retention following local delivery. Here, we develop a localized cytokine therapy that elicits profound anti-tumor immunity by engineered targeting to the ubiquitous leukocyte receptor CD45. We designed CD45-targeted immunocytokines (αCD45-Cyt) that, upon injection, decorated the surface of leukocytes in the tumor and tumor-draining lymph node (TDLN) without systemic exposure. αCD45-Cyt therapy eradicated both directly treated tumors and untreated distal lesions in multiple syngeneic mouse tumor models. Mechanistically, αCD45-Cyt triggered prolonged pSTAT signaling and reprogrammed tumor-specific CD8+ T cells in the TDLN to exhibit an anti-viral transcriptional signature. CD45 anchoring represents a broad platform for protein retention by host immune cells for use in immunotherapy.

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