Human Papillomavirus 16/18 E7-Pulsed Dendritic Cell Vaccination in Stage IB-IIA Cervical Cancer Patients; A Phase I Escalating Dose Trial     Free

LB-344

The safety and immunogenicity of HPV16 or HPV18 E7 antigen-pulsed mature dendritic-cell (DC) vaccination was evaluated in patients with stage IB or IIA cervical cancer. Escalating doses of autologous DC (5, 10 and 15 x 10⁶ for injection) were pulsed with recombinant HPV16 E7 or HPV18 E7 antigens and keyhole limpet hemocyanin (KLH, an immunological tracer molecule) and delivered in 5 subcutaneous injections at 21 day intervals to 10 cervical cancer patients with no evidence of disease after radical surgery. Safety, toxicity, delayed type hypersensitivity (DTH) reactions, and induction of serological and cellular immunity against HPV16/18 E7 and KLH were monitored. DC vaccination was well-tolerated, and no significant toxicities were recorded. All patients developed CD4+ T cell and antibody responses to DC vaccination, as detected by ELISpot and ELISA, respectively. Vaccine dose did not predict the magnitude of the antibody and T cell responses or the time to detection of HPV16/18 E7-specific immunity. DTH responses to intradermal injections of HPV E7 antigen and KLH were detected in all patients after vaccination. We conclude that HPV E7-loaded DC vaccination is safe and immunogenic in stage IB-IIA cervical cancer patients. Phase II E7-pulsed DC-based vaccination trials in cervical cancer patients harboring limited tumor burden, or at significant risk of tumor recurrence, are warranted. (BB-IND-11307; supported by NIH R21 CA094507 to AS).