Oncolytic Viruses in Peritoneal Cavity Cancer Treatment

Introduction of Peritoneal Cavity Cancer

Peritoneal cavity cancer is a rare type of cancer that spreads along the peritoneal surfaces to affect the peritoneum. The peritoneum tissues inside the wall of the abdomen are made of the thin layer of epithelial cells that allow organs to move smoothly inside the abdomen and protect the organs in the abdomen. Peritoneal cavity cancer has two forms, one is primary peritoneal cancer that starts in the peritoneum itself, and another is secondary peritoneal cancer that usually develops when existing abdominal cancers such as the appendix, colon, rectal, and pancreatic cancers into the peritoneum. This causes tumors to grow throughout the peritoneum. Cancers that spread to the lining surfaces of the peritoneal could be referred to as peritoneal carcinomatosis.

Symptoms

In its early stages, patients often have no apparent symptoms and do not notice symptoms until the disease is relatively advanced. The early symptoms often occur vague and nonspecific and hard to pinpoint, with abdominal swelling, abdominal pain, indigestion, and urinary frequency. As cancer progresses and a watery fluid (ascites) in the abdominal cavity, other symptoms occur, including nausea or vomiting, complete bowel or urinary blockage, abnormal vaginal bleeding, an abdominal mass, and shortness of breath.

Diagnosis and Treatment

Because the symptoms of peritoneal cancer undetected in the early stage, peritoneal cancer is often diagnosed at a late stage. Many different tests can be used to diagnose a patient with peritoneal carcinomatosis. By pelvic examination, tumor nodules in the abdomen or fluid (ascites) may sometimes be felt, but small tumors and microscopic cells sneak by undetected. Using blood tests and imaging studies such as CT scan, ultrasound, or MRI of the abdomen and pelvis can be used to check the tumor markers or to assess the extent of disease in the abdomen.

Based on specific cancer types and stages, some strategies can be used in the treatment of peritoneal cavity cancer to prevent cancer from spreading such as the surgery followed by chemotherapy. This technique, which combines surgery with chemotherapy which can shrink the tumor before surgery or kill any remaining cancerous cells after surgery, has a great promising treatment of peritoneal cavity cancers. In some cases, other clinical trials include targeted therapy, radiation therapy, hormonal therapy, and immunotherapy can be used to treat or prevent peritoneal cavity cancer without harming healthy cells.

Stage of primary peritoneal cancer. Fig.1 Stage of primary peritoneal cancer. (Height, 2019)

Oncolytic Viruses in Peritoneal Cavity Cancer Treatment

  • Herpes Simplex Virus
  • Herpes simplex virus-1 (HSV-1) oncolytic mutants are tropic for cancer cells, in which NV1066 replicates within tumor cells, expresses enhanced green fluorescent protein (EGFP), and kills gastric cancer and peritoneal cavity cancer. NV1066 has been efficacious in preclinical cancer models and is currently under evaluation in clinical trials. The clinical studies demonstrate that NV1066 is cytotoxic to human gastric cancer cells in vitro and in the model of disseminated peritoneal cancer in vivo. NV1066 has shown significant oncolytic activity in vitro and in vivo in order to eradicate carcinomatosis. Moreover, NV1066 induces EGFP expression in infected intraperitoneal tumor cells, which does not seem to diminish the anticancer activity of this oncolytic NV1066 but could help the laparoscopic visualization further to allow direct detection and localization of oncolytic viral therapy.

    G207 and NV1020 are two selectively replication oncolytic HSVs within tumor cells, and NV1020 is attenuated recombinant HSV. Both G207 and NV1020 are evaluated in the current studies for their anticancer effects in the treatment of gastric cancer. The results show that both G207 and NV1020 effectively infect, replicate, and kill cancer cells at lower concentrations in a murine model of peritoneally disseminated cancer. Oncolytic therapy using engineered HSVs have shown as a promising therapeutic strategy to facilitate diagnosis and track treatment response for peritoneal cavity cancer.

  • Vaccinia Virus
  • The oncolytic vaccinia virus is one of the prototype members of the genus Orthopoxvirus, which is a double-stranded DNA virus with the cytolytic capacity for a broad range of tumor cell types. The oncolytic vaccinia virus GL-ONC1 comprises three foreign integrated transgene cassettes (encoding Ruc-GFP, β-glucuronidase, and β-galactosidase) to disrupt the nonessential vaccinia genes. This GL-ONC1 is employed as a locoregional treatment in patients with advanced peritoneal carcinomatosis and enhances its tumor-selective targeting to spread across in the peritoneal cavity. In a phase I study, the recombinant GL-ONC1 is tested in patients to assess the safety and anti-tumor activity of intraperitoneal administration in advanced stage peritoneal cavity cancer patients. The results are shown that GL-ONC1 is well tolerated when administered into the peritoneal cavity of patients and no dose-limiting toxicities, and all adverse events are transient; it demonstrates that GL-ONC1 has the potential clinical efficacy and the biologic effects. Based on all the comprehensive data, it can be concluded that GL-ONC1 is both safe and efficient, which can be tested in further clinical studies and warrant the further development of the intraperitoneal route of virotherapy, especially for peritoneal cavity cancer.

Currently, engineered oncolytic viruses are emerging as attractive anticancer therapeutics with efficacy and safety in clinical trials due to their unique abilities. Creative Biolabs is one of the well-recognized experts who are professionals in oncolytic virus therapy development aided by our advanced OncoVirapy™ platform. With over a decade of extensive experience, our scientists are confident in accomplishing numerous challenging oncolytic virus construction and oncolytic virus engineering projects for our worldwide customers.

References

  1. Height, T. Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment (PDQ®): Treatment-Health Professional Information [NCI].
  2. Stanziale, S. F.; et al. Oncolytic herpes simplex virus-1 mutant expressing green fluorescent protein can detect and treat peritoneal cancer. Human gene therapy. 2004, 15(6):609-18.
  3. Lauer, U. M.; et al. Phase I study of oncolytic vaccinia virus GL-ONC1 in patients with peritoneal carcinomatosis. Clinical Cancer Research. 2018, 24(18):4388-98.
  4. Bennett, J. J.; et al. Comparison of safety, delivery, and efficacy of two oncolytic herpes viruses (G207 and NV1020) for peritoneal cancer. Cancer gene therapy. 2002, 9(11):935.
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