BVAC-C

This study sought to assess the relative effect of catheter, tissue, and catheter-tissue parameters, on the ability to determine the amount of viable myocardium in vivo.

Although multiple variables impact bipolar voltages (BVs), electrode size, interelectrode spacing, and directional dependency are of particular interest with the development of catheters incorporating mini and microelectrodes.

Nine swine with early reperfusion myocardial infarctions were mapped using the QDot catheter and then remapped using a Pentaray catheter. All QDot points were matched with Pentaray points within 5 mm. The swine were sacrificed, and mapping data projected onto the heart. Transmural biopsies corresponding to mapping points were obtained, allowing a comparison of electrograms recorded by mini, micro-, and conventional electrodes with histology.

The conventional BV of 2,322 QDot points was 1.9 ± 1.3 mV. The largest of the 3 microelectrode BVs (BV_µMax) average 4.8 ± 3.1 mV. The difference between the largest (BV_μMax) and smallest (BV_μMin) at a given location was 53.7 ± 18.1%. The relationships between both BV_μMax and BV_μMin and between the conventional BV and BV_μMax were positively related but with a significant spread in data, which was more pronounced for the latter. Pentaray points positively related to the BV_μMax with poor fit. On histology, increasing viable myocardium increased voltage, but both the slope coefficient and fit were best for BV_μMax.

Using histology, we could demonstrate that BV_μMax is superior to identify viable myocardium compared with BV_C and BV using the Pentaray catheter. The ability to simultaneously record 3 BV_μs with different orientations, for the same beat, with controllable contact and selecting BV_μMax for local BV may partially compensate for wave front direction.

: 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.