# Next Generation Gene-Gun Delivered DNA and RNA Immunotherapeutic Vaccines for Melanoma.

> **NIH NIH R43** · ORLANCE, INC. · 2024 · $200,000

## Abstract

PROJECT SUMMARY
Orlance has developed a next-generation Gene Gun (MACH-1 GG) that efficiently delivers DNA and RNA into
epidermal cells, leading to robust immune responses. Sequencing of tumors from individual patients has led to
the identification of personalized neoantigens that could be targeted with cancer vaccines. However,
technologies that can effectively deliver these cancer neoantigens and promote the induction of localized tumor
specific T cell responses are still needed. Nucleic acid (NA; DNA and RNA) vaccines administered using specific
formulations or delivery technologies that achieve intracellular delivery offer considerable promise to achieve
this goal. These include electroporation (EP) or jet injection for IM delivery of DNA or lipid nanoparticles (LNPs)
for IM delivery of RNA. These delivery modalities, however, have different drawbacks including a requirement
for high doses (1-5 mg of DNA), ultra-cold storage due to limited stability (RNA/LNPs), reactogenicity or pain
post-administration, and a limited ability to target immune responses to specific tissues. The GG entails the
delivery of room temperature stable lyophilized DNA or RNA vaccines on gold microparticles. It achieves painless
and direct intracellular delivery into skin cells with very low doses (1-4 µg) that results in systemic, mucosal and
localized skin immune responses that could provide a benefit for treatment of cancers and, in particular,
melanoma. The MACH-1 GG is based on a previous successful GG that induced strong antibody and T cell
responses in phase I human clinical trials. The MACH-1 provides significant improvements over this earlier
device. Here, we will investigate the feasibility of using MACH-1 to deliver DNA or RNA cancer vaccines in mice
and test the hypothesis that MACH-1 will offer advantages in immunogenicity and efficacy over other DNA/RNA
delivery technologies for melanoma. We will first determine if co-delivering a novel set of genetic adjuvants will
increase the ability of MACH-1 DNA and RNA vaccines to induce melanoma-specific T cell responses. Next, we
will determine if combining DNA and RNA in the same dose or in a prime-boost regimen offers synergistic effects.
We will then compare MACH-1 delivery of DNA and/or RNA melanoma vaccines to DNA delivery by EP or RNA
delivery by LNPs for immunogenicity and protective efficacy in mice. This work will be accomplished in two Aims:
Aim 1: Investigate the impact of genetic adjuvants on the immunogenicity and efficacy of GG delivered DNA and
RNA melanoma vaccines. Aim 2: Determine if combining the optimized adjuvanted DNA and RNA vaccines in
the same dose or in a prime-boost regimen enhances immunogenicity and efficacy compared to EP delivery of
DNA and LNP delivery of RNA in a mouse model of melanoma. Successful completion of these Aims will
establish MACH-1 as an effective device to deliver cancer vaccines.

## Key facts

- **NIH application ID:** 10932954
- **Project number:** 5R43CA281585-02
- **Recipient organization:** ORLANCE, INC.
- **Principal Investigator:** Hannah Frizzell
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $200,000
- **Award type:** 5
- **Project period:** 2023-09-21 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932954

## Citation

> US National Institutes of Health, RePORTER application 10932954, Next Generation Gene-Gun Delivered DNA and RNA Immunotherapeutic Vaccines for Melanoma. (5R43CA281585-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10932954. Licensed CC0.

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