New research, led by Connie Trimble, MD, shows that vaccine treatments for women with high-grade cervical dysplasia can trigger an immune response that may induce some lesions to resolve.
Vaccine treatments for women with high-grade precancerous cervical lesions triggered an immune cell response within the damaged tissue and caused some of the women’s cervical lesions to disappear, preliminary results of a small trial found.
The results, reported online in Science Translational Medicine, suggest that measuring immune system responses directly in the lesions may prove to be more accurate in evaluating therapeutic vaccines than traditional blood analysis.
- Preliminary findings showed that vaccine treatments for women with high-grade precancerous cervical lesions triggered an immune cell response within the damaged tissue that was not evident in blood samples.
- This ongoing study plans to enroll about 20 more women.
"It's difficult to measure immune cell responses to therapeutic vaccines, but we believe that clinical studies could tell us more about the value and function of the vaccines if we check for the response in the lesions, where the immune system is fighting precancerous cells," said Cornelia “Connie” Trimble, MD, associate professor of gynecology and obstetrics, oncology and pathology at Johns Hopkins' Kimmel Cancer Center and director of Johns Hopkins Center for Cervical Dysplasia.
The results involve 12 women, but researchers plan to continue the study by enrolling around 20 more women. Ongoing research will test a combination of the same vaccines and a topical cream to enhance the immune response locally.
For the preliminary study, the researchers enrolled women whose cervical lesions were linked to HPV serotype 16, a strain of the human papillomavirus most commonly associated with cervical cancer. The first woman was enrolled in 2008, with the last women being treated in 2012.
To treat the lesions and prevent cervical cancer, each woman received 3 vaccine injections in the upper arm over an 8-week period. Two vaccines were used for the study, including one made with genetically engineered DNA molecules that aim to teach immune system cells to recognize premalignant cells expressing E7 proteins of HPV serotype 16. The second vaccine was a noninfectious, engineered virus intended to kill precancerous cells marked by E6 and E7 proteins of HPV serotypes 16 and 18. Seven weeks after the final vaccination, the cervical lesions were removed from each woman.
Among those vaccinated, the investigators found significant increases in CD8+ T cells in cervical tissue. Yet, blood samples, which were collected at the beginning and end, failed to show as strong a pre- and post-vaccination effect.
"We found striking immune system changes within cervical lesions, which were not as evident in the patients' peripheral blood samples," Trimble explained.
Maldonado L, Teague JE, Morrow MP, et al. Intramuscular therapeutic vaccination targeting HPV16 induces T-cell responses that localize in mucosal lesions. Sci Transl Med. January 29, 2014. DOI: 10.1126/scitranslmed.3007323.