The vaccine, pNGVL4a-CRTE6E7L2, also showed signs of efficacy in patients living with HIV, reported Kimberly Lynn Levinson, MD, MPH, associate professor of obstetrics and gynecology at Johns Hopkins Medicine in Baltimore.
“We demonstrated a 78% rate of clearance for both histologic regression and HPV16, with some clearance of other HPV types,” she said in an oral abstract presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, held in San Diego.
Further evaluation of the vaccine in vulvar, vaginal, and other tissue types is required, and evaluation of immune response at the local and systemic is ongoing, Dr. Levinson said.
In contrast to HPV16 prophylactic vaccines, which form an antibody-specific response to HPV, therapeutic vaccines elicit a cell-mediated immunity, primarily focusing on the virus’ E6 and E7 proteins.
There are currently only three Food and Drug Administration–approved therapeutic vaccines for cancer, but none are as yet approved for treatment of gynecologic malignancies.
According to the US National Institutes of Health, there are multiple therapeutic HPV vaccines in development using either vector-based, peptide and protein-based, or nucleic-acid based approaches, or whole cell (dendritic cell) approaches.
Current Study
Dr. Levinson noted that “DNA vaccines are both well tolerated and simple to produce, and the addition of calreticulin enhances immune response.”
The investigational vaccine is delivered via an electoporation device (TriGrid delivery system) that stimulates muscle at the injection site to produce an enhanced immune response.
In preclinical studies the device was associated with an enhanced immune response compared with standard intramuscular injection. The enhance immune effect persisted despite CD4 T cell depletion.
The investigators conducted a phase 1 dose-escalation study, administering the vaccine to two separate cohorts: women without HIV who had HPV16-positive cervical dysplasia (CIN 2/3) and women living with HIV with HPV16-positive cervical or vulvovaginal dysplasia (CIN 2/3, VIN 2/3 or VAIN 2/3).
The vaccine was delivered at weeks 0, 4, and 8, at doses of 0.3 mg, 1.0 mg, or 3.0 mg. At week 12, all patients underwent site-specific biopsy to verify non-progression.
At 6 months, the patients then underwent definitive treatment with either loop electro excision or vulvar/vaginal excision. At 12 months, all patients had standard evaluations with biopsies.
Dr. Levinson reported results for the first 14 women enrolled, 10 of whom were HIV-negative and 4 of whom were HIV-positive.
Of nine women in the HIV-negative arm who had completed 6-month visits and were evaluable, two had HPV16 clearance by 2-month follow-up, and seven had clearance at 6 months. Other HPV subtypes cleared in two of five patients at 3 months and in three of five at 6 months.
In addition, seven of nine patients in this arm had histologic regression at 6 months.
In the HIV-positive arm, the two patients with CIN had no HPV16 clearance at 3 months, but both had clearance at 16 months. The vaccine did not clear other HPV subtypes in these patients, however.
Of the two women in this arm who had VIN, one had HPV16 clearance and histologic regression at 6 months. The other patient had neither viral clearance nor histologic regression.
All participants tolerated each vaccine well. Adverse events were all grade 1 in severity and resolved within 4 weeks. The most common event was tenderness at the injection site. There were also three cases of mild headache, two cases of drowsiness, and one of nausea.