# Targeted Gene Delivery and Human Dendritic Cell Maturation Through a Novel Hybrid Biological-Biomaterial Vector System

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2024 · $454,261

## Abstract

PROJECT SUMMARY
 The enclosed application presents an approach for effective dendritic cell (DC) genetic antigen delivery to
trigger cancer-specific immune reactivity, predicated upon the use of a “hybrid” biomaterial-biological delivery
vector featuring a bacterial core within a polymeric coating. Support for the impact of the proposed study
includes emerging research demonstrating advances in DC vaccination to prompt sustained immune response
outcomes (≥10 years) with improved patient survival in Phase II clinical trials and current open Phase III trials.
However, there remain challenges to broad efficacy in that most metastatic patients still do not respond to
treatment, thus, presenting an unmet need to improve these immune-based strategies. Compounding this
limitation are the standard methods currently utilized for antigen delivery to DCs, with poor immunotherapy
outcomes hypothesized to be the result of ineffectual means of antigen delivery that do not consider the
cellular-level challenges to DC activation and antigen transport. Systematically dealing with every aspect of DC
interaction and antigen delivery, in our view, will have transformative impact on the field of cancer
immunotherapy. In response, we propose the application of a biological-biomaterial hybrid vector specifically
designed for DC interfacial recognition and antigen delivery. In so doing, we put forth the hypothesis that this
technology will address current limitations with DC-based antigen delivery and subsequent immunotherapy
effectiveness. The research strategy presents a plan to systematically test this hypothesis through a series of
specific aims designed to better assess hybrid vector interaction with and activation of DC (Aim 1); evaluate
DC intracellular trafficking of the hybrid vector and final gene delivery effectiveness as a function of vector
design (Aim 2); and examine the impact of hybrid vector delivery on DC-mediated T cell activation in vivo (Aim
3). The enclosed project is supported by a well-qualified and complementary team of biological engineers and
cancer immunologists capable of positioning the results for translational impact.

## Key facts

- **NIH application ID:** 10793536
- **Project number:** 5R01CA270155-02
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Jason B Muhitch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $454,261
- **Award type:** 5
- **Project period:** 2023-03-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10793536

## Citation

> US National Institutes of Health, RePORTER application 10793536, Targeted Gene Delivery and Human Dendritic Cell Maturation Through a Novel Hybrid Biological-Biomaterial Vector System (5R01CA270155-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10793536. Licensed CC0.

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