# A Phase I Open Label, Dose Escalation Clinical Trial Assessing the Safety, Tolerability, and Feasibility of pNGVL4aCRTE6E7L2 HPV DNA Vaccine Administration Via Intramuscular TriGridTM Electroporation

> **NIH NIH P50** · JOHNS HOPKINS UNIVERSITY · 2024 · $322,209

## Abstract

Project Summary/Abstract
Surgical or ablative treatment of cervical cancer precursors, i.e., high-grade squamous intraepithelial
lesion (HSIL)/cervical intraepithelial neoplasia (CIN2/3), has reduced disease incidence but is
associated with increased rates of infectious complications, cervical incompetence with premature
deliveries, failure to clear HPV, and disease recurrence. Additionally, persistent HPV infection can
cause pre-invasive and invasive disease at other sites (vagina/vulva/anus) that are harder to treat. The
overall goal of Project 3 is to test the safety and toxicity of a therapeutic HPV vaccine, the CRTE6E7L2
DNA vaccine, delivered intramuscularly (IM) via the TriGrid Electroporation Device, in HIV- and HIV+
patients (including HIV- patients on the kidney transplant waitlist) who have HPV16-associated HSIL
lesions of the cervix (CIN), vagina (VaIN), and/or vulva (VIN). We will also examine virologic and
disease outcomes. HPV16 is the most common genotype in cervical cancer, and it dominates (> 85%)
in other anogenital and head and neck malignancies. HPV-related cancer incidence is significantly
elevated in patients living with HIV and in organ transplant recipients, both in the cervix and at other
sites. These patients acquire more frequent multi-genotype infections, including many of genotypes
that are less common in healthy individuals and that are not targeted by the current HPV preventive
vaccines. Our candidate therapeutic and preventive HPV vaccine, CRTE6E7L2, comprises the
pNGVL4a DNA vector encoding the heat shock protein calreticulin (CRT) fused genetically with HPV16
E6 and E7 (each obligately expressed in HPV malignancies) as well as the L2 capsid protein (a broadly
protective antigen). Fusion with CRT profoundly enhances the potency of DNA vaccines in generating
HPV antigen-specific CD8+ T cell-mediated immune responses, even in CD4-depleted animals.
CRTE6E7L2 DNA vaccination also induces L2-specific neutralizing antibodies and protects from
experimental vaginal challenge. These features make the CRTE6E7L2 DNA vaccine particularly
promising for use in patients living with HIV and transplant patients, which are both challenging groups
to treat. Although DNA vaccines are relatively safe and well suited for multiple administrations, in the
past, they have shown limited immunogenicity when administered alone by conventional intramuscular
needle injection, likely reflecting inefficient host cell transduction. In vivo electroporation is a much more
effective DNA vaccine administration method to generate HPV-specific CD8+ T cell immune responses.
Clinical responses to date have been highly encouraging in both HIV+ and HIV- patients. Our Specific
Aims in Project 3 are: (1) Evaluate the safety and toxicity of CRTE6E7L2 administered via
electroporation in HIV- and HIV+ patients with HPV16+ high-grade CIN/VaIN/VIN, including HIV-
patients on the kidney transplant waitlist; (2) Characterize the HPV16 E6/E7/L2-specific cell-
media...

## Key facts

- **NIH application ID:** 10935441
- **Project number:** 2P50CA098252-21
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Richard Bruce Roden
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $322,209
- **Award type:** 2
- **Project period:** 2003-09-30 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10935441

## Citation

> US National Institutes of Health, RePORTER application 10935441, A Phase I Open Label, Dose Escalation Clinical Trial Assessing the Safety, Tolerability, and Feasibility of pNGVL4aCRTE6E7L2 HPV DNA Vaccine Administration Via Intramuscular TriGridTM Electroporation (2P50CA098252-21). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10935441. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*