# Biomaterial Cancer Vaccines that Generate Patient-Specific Antigen In Situ

> **NIH NIH R01** · HARVARD UNIVERSITY · 2021 · $425,863

## Abstract

Cancer immunotherapies that exploit ex vivo manipulation of a patient's own cells can generate significant anti-
tumor immune responses, but present significant practical limitations. Nanoparticle-based antigen presenting
systems provide an alternative approach to generate anti-tumor responses without ex vivo cell manipulation,
but the defined antigens will likely need to be personalized to each patient. We have demonstrated a new
concept, the use of implantable biomaterials that can localize large numbers of dendritic cells (DCs) from the
host, and efficiently activate these cells while loading with antigens derived from a tumor biopsy. This
approach demonstrated unprecedented ability to promote regression of established tumors in several pre-
clinical models, and we have recently initiated a Phase I trial of this new approach to treat stage IV melanoma
patients. However, the antigen in this vaccine is derived from a biopsy, leading to the requirement that each
vaccine be manufactured for a specific patient, and the vaccine requires surgical implantation. This project is
based on the premise that combining delivery of traditional chemotherapeutic agents and biomaterial-
based vaccination will lead to therapeutic immune responses, by generating patient-specific antigen in
situ, obviating the need to identify or load antigen onto vaccines prior to placement in the body. Our
hypothesis will be tested using the following Aims: (1) Develop cryogels capable of being injected intra and/or
peritumorally that recruit DCs through GM-CSF release, and control the timing of release of nanoparticles
(NPs) containing toll like receptor ligands from the biomaterial vaccine in order to concentrate and activate DCs
within the tumor, and enhance their trafficking to the draining lymph node. (2) Determine the impact of an
approach to localize immunostimulatory chemotherapeutic agents to tumors on cancer cell death, and
determine the impact of combined chemotherapy and vaccination on tumor growth and the tumor-specific host
immune response. (3) Examine the ability of vaccination at the primary tumor to yield therapeutic effects on
distant tumors in the body, and combine the biomaterial-based vaccine strategy with checkpoint blockade
therapy. These studies will utilize both transplantable tumor models and a transgenic melanoma model. This
project will result in the development of a new, patient-specific vaccination strategy that does not
require personalized manufacturing. We expect this vaccine strategy will synergize with checkpoint
blockade therapy, yielding robust and systemic therapeutic benefit.

## Key facts

- **NIH application ID:** 10053676
- **Project number:** 5R01CA223255-04
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** David J Mooney
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $425,863
- **Award type:** 5
- **Project period:** 2017-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10053676

## Citation

> US National Institutes of Health, RePORTER application 10053676, Biomaterial Cancer Vaccines that Generate Patient-Specific Antigen In Situ (5R01CA223255-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10053676. Licensed CC0.

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