Clinical Trial of a Cancer Vaccine Targeting VEGF and KIF20A in Advanced Biliary Tract Cancer

Vaccine-specific CD8 T-cell responses. Representative results of the ELISPOT assay (day T29) for OCV-007, -008, and -004. “TISI (lymphoblast cells positive for HLA-A*24:02) + KIF20A” and “TISI+VR2” indicate stimulators with KIF20A and VR2 peptide pulses, respectively. “TISI” indicates stimulators alone, without a peptide pulse. R/S Ratio: responder/stimulator Ratio. All ELISPOT assays were performed in triplicate wells. The immune response is represented as positive or negative, the definition of which is detailed in “Materials and Methods” section. VR2, VEGFR2.

Comparison of survival between ELISPOT-positive and -negative cases. Kaplan–Meier estimates of progression-free survival (PFS) and overall survival (OS) in patients treated with OCV-C01, comparing ELISPOT-positive (+) (n=4, solid line) and -negative (–) (n=2, dotted line) groups. A log–rank test between positive and negative ELISPOT findings revealed that vaccine-specific T-cell responses were associated with significantly longer OS and PFS (p=0.0177).

TCR repertoire of vaccine-induced CD8 T cells. (a) TCRβ repertoire in ELISPOT-positive and -negative cases. We used bulk CD8+ T cells stimulated with the indicated peptides, as shown in the ELISPOT assay, to amplify TCRα,β chain cDNA and finally analyse the DNA sequence. Each pie chart colour indicates the T-cell population that expressed the same clonotypic TCRβ. The same color in different cases does not mean the same clone. Grey zone denotes the repertoire obtained from only a single T-cell clone. (b) Change in Diversity index of both TCRα and β of Vx-induced CD8 T cells. Dotted lines indicate TCRα; solid lines indicate TCRβ.