SHPC6 cell line细胞株 BioVector NTCC质粒载体菌种细胞基因保藏中心

SHPC6 cell line细胞株

Oncolytic adenoviruses (Ads) are a promising new modality in cancer treatment. We have developed a family of such vectors, and one of these vectors, INGN 007, is entering Phase I clinical trials. Below we report that INGN 007 is safe and efficacious in an orthotopic pancreatic cancer model. Oncolytic Ad vectors need to be tested in a permissive, immune competent model to assess all facets of the host-tumor-vector interaction. The Syrian hamster is such an animal model: Species C Ads replicate well in Syrian hamster tissues, and Syrian hamster cell lines are available that are known to support Ad5 replication. Thus, treatment of hamsters carrying tumors of hamster origin with oncolytic Ads mirrors what might happen in a human patient to a greater fidelity than previously used models based on immunodeficient mice. In this study, we established a new Syrian hamster cell line from a transplantable pancreatic tumor. This cell line, SHPC6, is highly permissive for Ad5 replication. The SHPC6 cell line formed disseminated intraperitoneal tumors when cells were injected into the peritoneal cavity, thus mimicking the presentation of end-stage pancreatic cancer in humans. The animals developed ascites and eventually succumbed to the disease (median survival time ca. 15 days). Intraperitoneal injection of INGN 007 completely reversed the growth of established disseminated intraperitoneal SHPC6 tumor nodules, resulting in 100% survival of the treated animals. Remarkably, many of the animals had already progressed to the stage when they had grossly visible ascites when they were injected with the vector. SHPC6 cells also formed subcutaneous tumors, whose growth was suppressed by INGN 007 following intratumoral injection. INGN 007 replication was detected by recovering and titering infectious particles in both the intraperitoneal and subcutaneous SHPC6 tumors. We have also developed a model, in which SHPC6 cells were injected directly into the pancreas and formed a more localized tumor within that organ. The growth of these tumors was followed by ultrasonic imaging, and the tumors were injected the tumors under real-time ultrasonic guidance. Importantly, intraperitoneal injection of INGN 007 was not hepatotoxic, and no virus replication was detected in the livers of INGN 007-injected hamsters bearing intraperitoneal SHPC6 tumors. We propose that the SHPC6 cell line in Syrian hamsters may be a valuable model for disseminated pancreatic cancer, and that the intraperitoneal injection of INGN 007 may be a safe and effective method to treat these tumors.

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