Integrated fluorescent cytology with nano‐biologics in peritoneally disseminated gastric cancer

Abstract

Gastric cancer patients positive for peritoneal cytology are at increased risk of tumor recurrence, but although a certain proportion of cytology‐positive patients relapse rapidly with aggressive progression, others survive longer with conventional chemotherapies. This heterogeneity makes it difficult to stratify patients for more intensive therapy and poses a substantial challenge for the implementation of precision medicine. We developed a new approach to identify biologically malignant subpopulations in cytology‐positive gastric cancer patients, using a green fluorescent protein (GFP)‐expressing attenuated adenovirus in which the telomerase promoter regulates viral replication (TelomeScan, OBP‐401). The fluorescence emitted from TelomeScan‐positive cells was successfully quantified using a multi‐mode microplate reader. We then analyzed clinical peritoneal washes obtained from 68 gastric cancer patients and found that patients positive for TelomeScan had a significantly worse prognosis. In 21 cytology‐positive patients, the median survival time of those who were TelomeScan positive (235 days) was significantly shorter than that for those who were TelomeScan negative (671 days; P = 0.0062). This fluorescent virus‐guided cytology detects biologically malignant cancer cells from the peritoneal washes of gastric cancer patients and may thus be useful for both therapy stratification and precision medicine approaches based on genetic profiling of disseminated cells.

Intraperitoneal cancer-immune microenvironment promotes peritoneal dissemination of gastric cancer

“…Peritoneal washes were obtained from GC patients during surgery performed in our hospital, 30,62 including 15 stage IV patients and 11 stage I patients. The samples were prospectively collected from all patients who gave their informed consent to participate in the study, and those used in this study were selected retrospectively and almost consecutively from the latest one, in consideration of the stock status and clinical stages.…”

Boosting Replication and Penetration of Oncolytic Adenovirus by Paclitaxel Eradicate Peritoneal Metastasis of Gastric Cancer

“…Previously, we developed an oncolytic Ad, OBP-401 (TelomeScan), which replicates selectively only within human cancer cells and expresses GFP. 21 , 23 To evaluate the antitumor effect of OBP-401 and PTX, which is effective for peritoneal metastasis of gastric and ovarian cancer following i.p. administration, 8 , 9 , 10 , 11 , 12 , 13 , 14 we treated GCIY or KATOIII cells with OBP-401 or PTX.…”

“… 16 , 18 , 19 , 20 , 31 Moreover, we have shown that i.p. administration of OBP-301 could spread to the peritoneal cavity and infect viable cancer cells, 23 , 32 resulting in antitumor effects on peritoneal metastasis. 28 …”

“… 20 We have further developed OBP-401 (TelomeScan), which is a modified OBP-301, to express green fluorescent protein (GFP) to visualize viable cancer cells. 21 , 22 , 23 OBP-401 enables detection of a few viable cancer cells as GFP-positive cells in the clinical peritoneal washes of advanced gastrointestinal cancer patients. 23 , 24 Although systemic virotherapy is impractical due to the presence of neutralizing antibodies for Ad, locoregional administration such as to an intratumoral site or the i.p.…”

Bone and Soft-Tissue Sarcoma: A New Target for Telomerase-Specific Oncolytic Virotherapy

“…Ex vivo experiments showed that the OBP-401-mediated GFP induction system detects a variety of tumor cells in clinical samples of blood [63][64][65][66][67][68][69][70][71][72][73] and in peritoneal washes [74][75][76] from cancer patients. Gastric cancer patients with GFP-positive peritoneal tumor cells show poor prognoses [74]. As OBP-401-mediated GFP induction depends on telomerase activity and CAR expression in tumor cells, this system is a useful method to detect CAR-positive sarcoma cells, but not to detect CAR-negative sarcomas or normal cells [61].…”