# Highly stable mini-circRNA vaccine with maximally activated and long-lasting T cells for HPV-related cancer combination immunotherapy

> **NIH NIH R43** · AMPEDRNA BIOSCIENCES LLC · 2024 · $398,823

## Abstract

Human papillomavirus (HPV) is responsible for a large proportion of global cancer cases, including head and
neck, cervical and anal cancers, among others. HPV-related cancers are caused by certain high-risk strains of
the virus, which can cause long-lasting infections that eventually lead to the development of cancerous changes.
The mainstay for addressing HPV-related cancer is prevention, particularly through prophylactic vaccination and
screening, and definitive treatment of early pre-cancerous lesions. Despite the success of prevention efforts, the
prevalence of early and late-stage HPV-related cancers is still staggering, with over 18,000 deaths annually in
the US. One promising new treatment approach is immunotherapy, in particular immune checkpoint inhibition
(ICI). However, only 15-30% of patients respond to ICI treatment, highlighting the need for new techniques to
boost efficacy. Although ex vivo adoptive T cell immunotherapies, in which human T cells are genetically modified
outside the body to target cancer cells, are promising, they have significant limitations due to complexity, cost,
and the need for myeloablative lymphodepletion. Effective therapeutic cancer vaccines have long been the holy
grail as potentially safe and cost-effective in vivo-elicited T cell therapies that could be used in all stages of
disease to boost cancer immunotherapy without the challenges and risks of ex vivo adoptive T cell therapies.
While conventional vaccines largely have not been effective, newer highly immunogenic mRNA cancer vaccines
have demonstrated clear evidence of efficacy with a reduction in recurrence and death in late-stage melanoma
and strong anti-tumor responses in pancreatic cancer. Mini-circular RNA (mcRNA) is a highly biostable
therapeutic cancer vaccine platform that can elicit robust activation and expansion of long-lasting antigen-specific
T cells, achieving breakthrough levels up to 8-fold higher than state-of-the-art mRNA vaccines with, surprisingly,
improved safety and tolerability. Our goal is to develop a highly immunogenic HPV E6 and E7 mcRNA vaccine
that could be used as an off-the-shelf HLA-agnostic product or as part of a personalized HLA-specific cancer
vaccine. In this proposal, we plan to build on a significant body of highly encouraging in vitro and in vivo data to
facilitate rapid development of the mcRNA therapeutic vaccine platform with a highly immunogenic vaccine for
HPV-related cancers. Key results from the proposed investigational studies will demonstrate the superior efficacy
of a LNP-encapsulated multivalent mcRNA HPV16 E6/E7 vaccine compared to a N1-methylΨ mRNA vaccine.
In Aim 1, we will show that a multivalent HPV mcRNA vaccine can sustain the expression of long concatemers
of encoded HPV E6/E7 epitopes that are processed and presented to elicit highly potent and durable T cell
responses that can yield a robust immunotherapy in combination with ICI for HPV-related cancer in mice. In Aim
2, we will characterize...

## Key facts

- **NIH application ID:** 10921006
- **Project number:** 1R43CA287530-01A1
- **Recipient organization:** AMPEDRNA BIOSCIENCES LLC
- **Principal Investigator:** Gordon Parry
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $398,823
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10921006

## Citation

> US National Institutes of Health, RePORTER application 10921006, Highly stable mini-circRNA vaccine with maximally activated and long-lasting T cells for HPV-related cancer combination immunotherapy (1R43CA287530-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10921006. Licensed CC0.

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