Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Dr, Tampa, FL, 33612, USA.
Cancer Biology Ph.D. Program, University of South Florida, Tampa, FL, USA.
BMC Cancer. 2021 Jun 30;21(1):756. doi: 10.1186/s12885-021-08522-z.
Chemotherapy regimens that include the utilization of gemcitabine are the standard of care in pancreatic cancer patients. However, most patients with advanced pancreatic cancer die within the first 2 years after diagnosis, even when treated with standard of care chemotherapy. This study aims to explore combination therapies that could boost the efficacy of standard of care regimens in pancreatic cancer patients.
In this study, we used PV-10, a 10% solution of rose bengal, to induce the death of human pancreatic tumor cells in vitro. Murine in vivo studies were carried out to examine the effectiveness of the direct injection of PV-10 into syngeneic pancreatic tumors in causing lesion-specific ablation. Intralesional PV-10 treatment was combined with systemic gemcitabine treatment in tumor-bearing mice to investigate the control of growth among treated tumors and distal uninjected tumors. The involvement of the immune-mediated clearance of tumors was examined in immunogenic tumor models that express ovalbumin (OVA).
In this study, we demonstrate that the injection of PV-10 into mouse pancreatic tumors caused lesion-specific ablation. We show that the combination of intralesional PV-10 with the systemic administration of gemcitabine caused lesion-specific ablation and delayed the growth of distal uninjected tumors. We observed that this treatment strategy was markedly more successful in immunogenic tumors that express the neoantigen OVA, suggesting that the combination therapy enhanced the immune clearance of tumors. Moreover, the regression of tumors in mice that received PV-10 in combination with gemcitabine was associated with the depletion of splenic CD11bGr-1 cells and increases in damage associated molecular patterns HMGB1, S100A8, and IL-1α.
These results demonstrate that intralesional therapy with PV-10 in combination with gemcitabine can enhance anti-tumor activity against pancreatic tumors and raises the potential for this strategy to be used for the treatment of patients with pancreatic cancer.
含吉西他滨的化疗方案是胰腺癌患者的标准治疗方法。然而，大多数晚期胰腺癌患者在诊断后 2 年内死亡，即使接受标准治疗化疗也是如此。本研究旨在探索能够提高胰腺癌患者标准治疗方案疗效的联合治疗方法。
在这项研究中，我们使用 PV-10（10%玫瑰红 Bengal 溶液）在体外诱导人胰腺肿瘤细胞死亡。进行了小鼠体内研究，以检查将 PV-10 直接注射到同种异体胰腺肿瘤中是否能导致病变特异性消融。在荷瘤小鼠中，将瘤内 PV-10 治疗与全身吉西他滨治疗相结合，以研究治疗肿瘤和未注射肿瘤的远端肿瘤的生长控制情况。在表达卵清蛋白 (OVA) 的免疫原性肿瘤模型中，研究了肿瘤免疫介导清除的参与情况。
在这项研究中，我们证明了将 PV-10 注射到小鼠胰腺肿瘤中会导致病变特异性消融。我们表明，将瘤内 PV-10 与全身吉西他滨联合使用会导致病变特异性消融并延迟未注射肿瘤的远端生长。我们观察到，这种治疗策略在表达新抗原 OVA 的免疫原性肿瘤中更为成功，表明联合治疗增强了肿瘤的免疫清除。此外，接受 PV-10 联合吉西他滨治疗的小鼠肿瘤的消退与脾 CD11bGr-1 细胞耗竭以及损伤相关分子模式 HMGB1、S100A8 和 IL-1α 的增加有关。
这些结果表明，PV-10 瘤内治疗联合吉西他滨可以增强对胰腺肿瘤的抗肿瘤活性，并为该策略用于治疗胰腺癌患者提供了潜力。
