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

Abstract

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.

Connecting METTL3 and intratumoural CD33+ MDSCs in predicting clinical outcome in cervical cancer

“…However, there are no confirmed molecular markers for tumour progression or prognosis in CC patients. The related viral proteins E6 and E7 have been the focal points of research for the past several years [11,12]. In other words, easily detectable and meaningful molecular markers need to be confirmed.…”

Efficacy and Safety of Immunotherapy for Cervical Cancer—A Systematic Review of Clinical Trials

“…A total of 25 trials were identified assessing therapeutic vaccines in cervical cancer patients [ 21 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ], of which 4 were not specific to cervical cancer but included a larger population with various cancers. The trials were published between 1989 and 2020.…”

A New Generation of Vaccines in the Age of Immunotherapy

“…Immunologic response analysis showed that BVAC-C induced activation of natural killer T cells, natural killer cells, and HPV E6/ E7 specific CD4 and CD8 T cells upon vaccinations in all patients evaluated. A phase II study is underway [36], as it is a phase I study of BVAC-B, transfected with recombinant HER2/neu, in patients with gastric cancer [37].…”