Fig. 2: INO-3107 induces peripheral T-cell responses in all patients.

A Interferon-gamma ELISpot T-cell response displayed as peak log₂ fold change above pretreatment responses against the HPV-6 (open black circles) and HPV-11 (open black squares) components for N = 32 patients, each represented by a symbol. Box and whiskers extend from 25th–75th percentile and minima to maxima, respectively; line at median, + at mean. B Top left panel: Representative staining of markers assessed for lytic granule loading (LGL) in HPV-specific multiparametric flow cytometry of CD8 + T-cells. Percentile of indicated cell populations are noted in each quadrant. Top right panel: peak frequency (%) of HPV-specific cytotoxic CD8 + T-cells (CTLs) above pretreatment responses as determined by flow cytometry and observed for N = 32 study patients, each represented by an open black diamond. Values at zero represent true zero values as well as negative values normalized to zero based on Y axis description. Box and whiskers extend from 25th–75th percentile and minima to maxima, respectively; line at median, + at mean. Bottom left panel: Peripheral T-cell profiling employing uniform manifold approximation and projection (UMAP) on all CD8 + T-cells and with activation, antigen experience, and effector marker identification, as determined by flow cytometry at Week 26 for n = 29 patients; no Week 26 data available for three patients. Bottom right panel: Heatmap of HPV-specific peak changes (Δ) in frequencies (%) of indicated parameters of CD8 + T-cells grouped by clinical response, as determined by flow cytometry. Infecting strain(s) of HPV noted in papilloma tissue are also indicated for n = 31 patients; one outlier is absent for improved visualization. C Left panel: Longitudinal frequency (%) of significantly expanded T-cell clonal populations as defined by CloneTrack for n = 27 patients, each represented by an open black diamond at any timepoint. Data were normalized to Screening (pretreatment) to specifically visualize on-study clonal expansion. Line denotes point-to-point geometric mean. Right panel: Absolute number of unique significantly expanded clonal populations observed during the study on a per-patient basis for n = 27 patients, each represented by an open black diamond. D Tracking of CDR3 clonotypes longitudinally across the study via Immunarch. Representative patient shown. E Break out of peripheral T-cell response frequencies by assay and in aggregate. log logarithm, HPV human papillomavirus, IFN-γ interferon-gamma, SFU spot forming units, Grz granzyme, Prf perforin, Gnly granulysin, TCRβ T-cell receptor beta chain, PBMC peripheral blood mononuclear cells, N number of patients, % percentile.