Human papillomavirus (HPV)-associated neoplasia of the cervix presents a compelling opportunity to test antigen-specific vaccination because expression of two nonself, viral antigens, E6 and E7, are together functionally required to initiate and maintain neoplastic lesions, both high grade dysplasia (CIN2/3), the precursor to invasive cancer, and cancer. This phase I clinical trial will assess the safety, tolerability, and immunogenicity of particle-mediated epidermal delivery (PMED) of a DNA vaccine which is targeted at the HPV16 E7 antigen, pNGVL4a-CRT-E7(detox), in patients with operable Stage IB1 cervical cancer associated with HPV16, the HPV genotype most commonly associated with disease. Clinical grade vaccine has been manufactured by NCI RAID, and has been formulated for PMED vaccination. This trial will also present a unique opportunity to assess the tumor compartment for molecular evidence of mechanisms of immune regulation, in specimens obtained at the time of standard therapeutic resection. Although the central assumption in designing immunotherapeutic strategies is that eliciting effector immune responses specific for tumor associated antigens will result in clinical response, it is clear from measures of HPV-specific immune responses in patients with HPV disease that the presence of immune responses in the peripheral blood does not always correlate with outcome. Therefore in this trial we will assess not only the safety and immunogenicity of vaccination in this patient cohort, but also determine whether measures of immune regulation in the tumor compartment correlate with ability to respond to vaccination. We have a demonstrated track record in clinical trial design and execution in this patient population, which is disproportionately comprised of minority women who do not access the medical care system effectively. This protocol will translate early development supported by the NCI SPORE mechanism, and take advantage of a longstanding collaboration with GOG investigators at the University of Alabama. This phase I clinical trial will test safety, feasibility, and immunogenicity of needle- free particle-mediated vaccination with a therapeutic HPV vaccine, pNGVL4a- CRT-E7(detox), in patients with operable Stage IB1 cervical cancer. This trial will also present a unique opportunity to assess the tumor compartment for evidence of mechanisms of immune regulation, in specimens obtained at the time of standard therapeutic resection. Clinical grade vaccine has been manufactured by NCI RAID, in collaboration with PowderMed. This trial is a SPORE-GOG collaboration. ? ? ?
