Journal of Clinical Medicine (Jan 2020)

Phase I Study of a B Cell-Based and Monocyte-Based Immunotherapeutic Vaccine, BVAC-C in Human Papillomavirus Type 16- or 18-Positive Recurrent Cervical Cancer

  • Chel Hun Choi,
  • Hyun Jin Choi,
  • Jeong-Won Lee,
  • Eun-Suk Kang,
  • Duck Cho,
  • Byung Kwan Park,
  • Yong-Man Kim,
  • Dae-Yeon Kim,
  • Hyungseok Seo,
  • Myunghwan Park,
  • Wuhyun Kim,
  • Ki-Young Choi,
  • Taegwon Oh,
  • Chang-Yuil Kang,
  • Byoung-Gie Kim

DOI
https://doi.org/10.3390/jcm9010147
Journal volume & issue
Vol. 9, no. 1
p. 147

Abstract

Read online

BVAC-C is a B cell-based and monocyte-based immuno-therapeutic vaccine transfected with a recombinant human papillomavirus (HPV) 16/18 E6/E7 gene and loaded with alpha-galactosyl ceramide, which is a natural killer T cell ligand. This phase I study sought to determine the tolerability and immunogenicity of BVAC-C in platinum-resistant recurrent cervical cancer patients. Patients with HPV 16-positive or 18-positive recurrent or persistent cervical cancer who had received at least one prior platinum-based combination chemotherapy were enrolled. BVAC-C was injected intravenously three times every four weeks, and dose escalation was planned in a three-patient cohort design at doses of 1 × 107, 4 × 107, or 1 × 108 cells/dose. Eleven patients were enrolled, and six (55%) patients had received two or more lines of platinum-based chemotherapy prior to enrollment. Treatment-related adverse events (TRAEs) were observed in 21 cycles. Most TRAEs were mild fever (n = 6.55%) or myalgia (n = 4.36%). No dose-limiting toxicities occurred. The overall response rate was 11% among nine patients evaluable, and the duration of response was 10 months. Five patients (56%) achieved a stable disease for 4.2−11 months as their best overall response. The median progression-free survival in all patients was 6.8 months (95% CI, 3.2 to infinite months), and the overall survival rate at 6 and 12 months was 89% (95% CI, 71 to 100%) and 65% (95% CI, 39 to 100%), respectively. BVAC-C induced the activation of natural killer T cells, natural killer cells, and HPV 16/18 E6/E7-specific T cells upon vaccination in all patients evaluated. BVAC-C was well tolerated and demonstrated a durable anti-tumor activity with an immune response in HPV 16-positive or 18-positive recurrent cervical carcinoma patients. A Phase 2 efficacy trial is currently underway.

Keywords