Fig. 4: Abscopal effect of combination therapy of GEM and nab-PTX with OBP-702 in a PAN02 bilateral subcutaneous tumor model.
a C57BL/6 mice bilaterally bearing PAN02 subcutaneous tumors were treated with GN (GEM 50 mg/kg, nab-PTX 5 mg/kg) intraperitoneally and/or OBP-702 (5 × 107 PFU) intratumorally once a week for 3 weeks, and sacrificed 34 days after initial treatment. OBP-702 was injected into the bigger tumor. Tumor volume was monitored (n = 7). The left figure shows tumor volume of the OBP-702-injected side, and the right figure shows the tumor volume of the OBP-702-uninjected side. b Anti-CD8α antibody was additionally injected into the peritoneal cavity once a week for 4 weeks, and tumor volume of control and OBP-702 with or without anti-CD8α antibody was monitored until 28 days after the initial treatment (n = 3–7). c, d The spleens harvested 14 days after the initial treatment were subjected to flow cytometry for SLECs, MPECs, TEMps, and TCMps. Representative figures of flow cytometry are shown in (c), in which CD3+/CD8+ cells are analyzed in the upper figures, and CD3+/CD8+/CD127+ cells are analyzed in the lower figures. Populations of SLECs, MPECs, TEMps, and TCMps are compared (n = 5) (d). e, f PAN02 tumors harvested 34 days after the initial treatment were subjected to flow cytometry for CD8+ cells and TRMs. Representative figures of flow cytometry are shown in (e), in which live cells are analyzed in the upper figures, and CD8+/CD45+ cells are analyzed in the lower figures. Populations of CD8+ cells and TRMs in OBP-702-injected tumors and OBP-702-uninjected tumors are compared (n = 3–7) (f). g, h The spleens harvested 34 days after the initial treatment were subjected to flow cytometry for TEMs and TCMs. Representative figures of flow cytometry are shown in (g), in which CD3+/CD8+ cells are analyzed. Populations of TEMs and TCMs are compared (n = 7) (h). *P < 0.05, **P < 0.005, ***P < 0.001. Con control, GN gemcitabine + nab-paclitaxel, 702 OBP-702, SLEC short-lived effector T cell, MPEC memory precursor effector cell, TEMp effector memory precursor cell, TCMp central memory precursor cell, TRM tissue-resident memory T cell, TEM effector memory T cell, TCM central memory T cell.
