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Peer-reviewedCC BY-NC 4.0Cell Reports Medicine

Spatially tuned localization of interleukins and OX40 agonists enhances synergistic anti-tumor immunity

  • John H. Klich1
  • Anahita Nejatfard2
  • Emily L. Meany1
  • Ben S. Ou1
  • Zuzanna D. Krawczyk3
  • Julie Baillet3
  • Eric A. Appel1,3,4,5,6
6 affiliations
  1. 1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
  2. 2Department of Biochemistry, Stanford University, Stanford, CA 94305, USA
  3. 3Department of Material Science and Engineering, Stanford University, Stanford, CA 94305, USA
  4. 4Sarafan ChEM- H, Stanford University, Stanford, CA 94305, USA
  5. 5Wood Institute for the Environment, Stanford University, Stanford, CA 94305, USA
  6. 6Department of Pediatrics (Endocrinology), Stanford University, Stanford, CA 94305, USA
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Abstract

While advances in immunotherapy have revolutionized care for cancer patients, most approaches still fail to mount a robust anti-cancer effect. To address this challenge, the field has turned to combination immunotherapies, but systemic administration of potent combination therapies has resulted in severe immune-related adverse effects. Here, we use an injectable polymer-nanoparticle (PNP) hydrogel to rationally localize immunotherapeutic cytokines (IL-12 and IL-2) intratumorally and antibodies (OX40a) peritumorally. We hypothesize that selectively altering the biodistribution of these cargo enables tolerable and synergistic anti-cancer combinations. Using in vivo imaging, we demonstrate that administration sites are critical for redistributing cargo to either the tumor or tumor-draining lymph node (tdLN). Further, we demonstrate that this approach synergistically improved treatment efficacy in the B16F10 and MC38 tumor models and alters cellular phenotypes, resulting in significant tumor clearance in both single and double tumor models.

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Cite

BibTeXRIS
BibTeX
@article{klich2026spatially,
  title = {{Spatially tuned localization of interleukins and OX40 agonists enhances synergistic anti-tumor immunity}},
  author = {John H. Klich and Anahita Nejatfard and Emily L. Meany and Ben S. Ou and Zuzanna D. Krawczyk and Julie Baillet and Eric A. Appel},
  journal = {Cell Reports Medicine},
  year = {2026},
  month = oct,
  doi = {10.1016/j.xcrm.2026.103109},
  url = {https://doi.org/10.1016/j.xcrm.2026.103109},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Spatially tuned localization of interleukins and OX40 agonists enhances synergistic anti-tumor immunity
AU  - John H. Klich
AU  - Anahita Nejatfard
AU  - Emily L. Meany
AU  - Ben S. Ou
AU  - Zuzanna D. Krawczyk
AU  - Julie Baillet
AU  - Eric A. Appel
PY  - 2026
DA  - 2026/10/09
JO  - Cell Reports Medicine
DO  - 10.1016/j.xcrm.2026.103109
UR  - https://doi.org/10.1016/j.xcrm.2026.103109
AB  - While advances in immunotherapy have revolutionized care for cancer patients, most approaches still fail to mount a robust anti-cancer effect. To address this challenge, the field has turned to combination immunotherapies, but systemic administration of potent combination therapies has resulted in severe immune-related adverse effects. Here, we use an injectable polymer-nanoparticle (PNP) hydrogel to rationally localize immunotherapeutic cytokines (IL-12 and IL-2) intratumorally and antibodies (OX40a) peritumorally. We hypothesize that selectively altering the biodistribution of these cargo enables tolerable and synergistic anti-cancer combinations. Using in vivo imaging, we demonstrate that administration sites are critical for redistributing cargo to either the tumor or tumor-draining lymph node (tdLN). Further, we demonstrate that this approach synergistically improved treatment efficacy in the B16F10 and MC38 tumor models and alters cellular phenotypes, resulting in significant tumor clearance in both single and double tumor models.
SN  - 2666-3791
ER  -