# Tumor-Associated Antigen Delivery using Protein Nanoparticles for Combined Immunotherapy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $330,747

## Abstract

PROJECT SUMMARY / ABSTRACT
 Enthusiasm for anti-tumor immunotherapy has increased dramatically with the clinical success
of immune checkpoint inhibitors (e.g., anti-PD-1, anti-CTLA-4) across diverse tumor types.
Checkpoint inhibitors release normal immune homeostatic mechanisms that impair the anti-tumor
immune response. Despite the promise of this approach, the majority of patients do not achieve long-
term remission and many cancer types do not respond to this type of therapy, felt to be due in part to
inadequate education of the immune system to the relevant tumor-associated antigens. Priming the
immune system during checkpoint inhibition therapy to better recognize tumor-associated antigens
(TAAs), using cancer vaccines, is an attractive option for improving outcomes.
 A major challenge for conventional cancer vaccines, however, is their potency. To address
this, TAAs have been delivered using a protein nanoparticle platform, E2, and this strategy has been
shown to elicit antigen-specific destruction of cancer cells and to significantly extend survival time for
tumor-bearing mice. The overall hypothesis of this proposed work is that by combining the synergistic
mechanisms of increasing antigen-specific effects using the E2 nanoparticle, while simultaneously
releasing the brakes on immune checkpoints, a better outcome will be achieved which prolongs
survival time and sustains anti-tumor immune responses. To test this hypothesis, we propose the
following specific aims: (1) Elucidate nanoparticle design and delivery strategies that will increase
anti-tumor responses, and determine the mechanisms of elicited anti-tumor activity; (2) Examine the
scope of E2-based vaccine efficacy by confirming activity in another tumor model in vivo and
evaluating human immune responses ex vivo; and (3) Evaluate the therapeutic combination of E2-
based vaccine formulations with a prototypical checkpoint inhibitor, anti-PD1, for enhanced anti-tumor
immune response.
 This work will evaluate whether more effective immunotherapy can be achieved by increasing
tumor antigen-specific responses (via E2 nanoparticle vaccines) while simultaneously blocking the
checkpoints to remove immune suppression (via immune checkpoint inhibition). These studies will
generate general principles for improving cancer treatment using such combination therapies.
Ultimately, it can potentially provide a more effective therapeutic strategy applicable for cancer states
that are conventionally difficult to treat.

## Key facts

- **NIH application ID:** 10063869
- **Project number:** 5R01EB027797-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Szu-Wen Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $330,747
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063869

## Citation

> US National Institutes of Health, RePORTER application 10063869, Tumor-Associated Antigen Delivery using Protein Nanoparticles for Combined Immunotherapy (5R01EB027797-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10063869. Licensed CC0.

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