# Local Administration of Particle-Anchored Cytokines as a Safe and Effective Cancer Immunotherapy

> **NIH NIH R21** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2024 · $379,981

## Abstract

PROJECT SUMMARY / ABSTRACT
The primary objective of this proposal is to develop a localized cancer immunotherapy using particle-anchored
cytokines with prolonged intratumoral retention to elicit durable anti-tumor immune responses. It is well known
that immunostimulatory cytokines can elicit robust anti-tumor immune responses in preclinical studies but also
exhibit severe immune-related adverse events due to systemic exposures. The current drug delivery
methodology cannot sustainably supply cytokines for days to weeks, failing to fully address issues of toxicity and
limited efficacy. We hypothesize that anchoring cytokines to large-sized particles for intratumoral injection would
enhance the local retention of cytokines (e.g., IL-12 and IL-15) to drive tumor inhibition while avoiding the
systemic exposures of such cytokines that cause adverse effects. To test this hypothesis, we develop a novel
local delivery system that physically anchors the Fc-cytokine to particles having surface-decorated Fc-binding
peptides. Our preliminary studies show that the intratumoral administration of our new particle-anchored cytokine
significantly increases tumor retention of cytokines and markedly reduces systemic toxicity. Moreover, local
treatments of our micron-meter-sized particle-anchored cytokines promote cures in poorly immunogenic tumor
models, and elicit anti-tumor immunities with controls over distant untreated lesions. Overall, two specific aims
will be pursued in this proposal, including: (i) to develop liposome-anchored cytokines with prolonged tumor
retention over one week and minimal systemic leakage of free cytokines; and (ii) to elucidate the mechanisms
by which particle-anchored cytokines elicit durable anti-tumor immunity to improve efficacies in poorly
immunogenic tumors. Our simple formulation technology would fully address the dose-limiting toxicity problem
in the use of cytokines in cancer immunotherapy, and provide a new and effective treatment option for difficult-
to-treat solid tumors when combined with other immunotherapeutics. This work will also advance the research
on drug delivery technology by elucidating crucial physicochemical characteristics to circumvent systemic
leakage for local drug delivery. This work will also significantly advance our understanding of how localized
immunostimulatory cytokines impact tumor microenvironments, leading to enhanced systemic anti-tumor
immunity and better treatment outcomes.

## Key facts

- **NIH application ID:** 10987601
- **Project number:** 1R21CA287324-01A1
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Rong Tong
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $379,981
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10987601

## Citation

> US National Institutes of Health, RePORTER application 10987601, Local Administration of Particle-Anchored Cytokines as a Safe and Effective Cancer Immunotherapy (1R21CA287324-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10987601. Licensed CC0.

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