# Localized immunotherapy using alum-binding therapeutics

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $522,925

## Abstract

Project Summary/Abstract
Combination treatments aiming to stimulate synergistic immune pathways employing cytokines or
immunomodulatory antibodies are generally more effective than monotherapies in preclinical models of cancer
immunotherapy. However when given systemically, these combination treatments suffer from high toxicity from
on-target off-tumor stimulation as well as low local concentrations at the tumor site due to poor tumor penetrance
and high clearance rates. Local intratumoral therapy is a viable approach to bypass some of the challenges
associated with systemic delivery, but requires optimization to promote retention of the therapeutic agent at the
injection site and minimize leakage into the circulation. We have recently developed an approach to enhance
vaccine efficacy by engineering the binding of immunogens to the commonly used adjuvant aluminum hydroxide
(alum) via a site-specific phosphoserine (pSer) peptide tag. The pSer moieties undergo a ligand-exchange
reaction with free hydroxyl groups on the surface of alum leading to stable anchoring of proteins on alum
particles. We propose here to apply this alum-anchoring platform in the context of cancer to retain potent immune
agonists within the tumor site, promoting a robust systemic immune response with minimal toxicity. Our
preliminary results show that this simple approach can be used to load stimulatory cytokines onto alum for
retention at the tumor site up to a month, stimulating a strong anti-tumor response from a single shot treatment.
We plan to develop and optimize this translational strategy through the following specific aims: (1) use in-cell
phosphorylation to produce phosphoserine-tagged cytokines and other candidate immune agonists for optimal
alum binding, (2) determine optimal treatment regimens for these intratumoral alum-bound therapeutic agents in
vivo in multiple tumor models, (3) define the mechanism of action through which this therapy elicits a response,
(4) evaluate the systemic immune response and assess strategies to enhance abscopal effects by promoting
the transfer of immunostimulatory payloads to motile lymphocytes for trafficking to distal untreated tumors.
These studies will establish a robust technology platform capable of safely delivering treatments currently viewed
as too toxic, by addressing key limitations in existing localized therapeutic strategies

## Key facts

- **NIH application ID:** 10367044
- **Project number:** 1R01EB031082-01A1
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Darrell J Irvine
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $522,925
- **Award type:** 1
- **Project period:** 2021-09-30 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367044

## Citation

> US National Institutes of Health, RePORTER application 10367044, Localized immunotherapy using alum-binding therapeutics (1R01EB031082-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10367044. Licensed CC0.

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