Effect of Systemic or Intraperitoneal Administration of Anti-PD-1 Antibody for Peritoneal Metastases from Gastric Cancer

Kumagai, Yuko; Futoh, Yurie; Miyato, Hideyo; Ohzawa, Hideyuki; Yamaguchi, Hironori; Saito, Shin; Kurashina, Kentaro; Hosoya, Yoshinori; Lefor, Alan Kawarai; Sata, Naohiro; Kitayama, Joji

doi:10.21873/invivo.12811

Cited by 13 publications

(10 citation statements)

References 59 publications

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“…Optimal treatment schedules are lacking and are hampered by the heterogeneity of evidence. Intraperitoneal immunotherapy, such as checkpoint inhibitors or tumor-specific antibodies, might be a promising route for in the future, but current evidence is confined to animal-studies only [62,63]. To generalize the use of intraperitoneal chemotherapy and to determine the optimal drug combination, studies directly comparing different regimens are warranted.…”

Section: Discussionmentioning

confidence: 99%

“…These novel methods might enhance intraperitoneal drug delivery by prolonging its local exposure, but no clinical or pharmacokinetic studies in patients with unresectable peritoneal disease have been performed so far. Intraperitoneal immunotherapy (anti-PD-1 therapy) has been studied in vivo for intraperitoneal use [62,63]. A cellular immune response has been shown in mouse models and might therefore have potential as an intraperitoneal drug, but as yet, no pharmacokinetic or clinical data are available demonstrating this rationale.…”

Section: Novel Intraperitoneal Agentsmentioning

confidence: 99%

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Intraperitoneal Chemotherapy for Unresectable Peritoneal Surface Malignancies

Guchelaar

Noordman

Koolen

et al. 2023

Drugs

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Malignancies of the peritoneal cavity are associated with a dismal prognosis. Systemic chemotherapy is the gold standard for patients with unresectable peritoneal disease, but its intraperitoneal effect is hampered by the peritoneal-plasma barrier. Intraperitoneal chemotherapy, which is administered repeatedly into the peritoneal cavity through a peritoneal implanted port, could provide a novel treatment modality for this patient population. This review provides a systematic overview of intraperitoneal used drugs, the performed clinical studies so far, and the complications of the peritoneal implemental ports. Several anticancer drugs have been studied for intraperitoneal application, with the taxanes paclitaxel and docetaxel as the most commonly used drug. Repeated intraperitoneal chemotherapy, mostly in combination with systemic chemotherapy, has shown promising results in Phase I and Phase II studies for several tumor types, such as gastric cancer, ovarian cancer, colorectal cancer, and pancreatic cancer. Two Phase III studies for intraperitoneal chemotherapy in gastric cancer have been performed so far, but the results regarding the superiority over standard systemic chemotherapy alone, are contradictory. Pressurized intraperitoneal administration, known as PIPAC, is an alternative way of administering intraperitoneal chemotherapy, and the first prospective studies have shown a tolerable safety profile. Although intraperitoneal chemotherapy might be a standard treatment option for patients with unresectable peritoneal disease, more Phase II and Phase III studies focusing on tolerability profiles, survival rates, and quality of life are warranted in order to establish optimal treatment schedules and to establish a potential role for intraperitoneal chemotherapy in the approach to unresectable peritoneal disease. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-022-01828-7.

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Section: Discussionmentioning

confidence: 99%

Section: Novel Intraperitoneal Agentsmentioning

confidence: 99%

Intraperitoneal Chemotherapy for Unresectable Peritoneal Surface Malignancies

Guchelaar

Noordman

Koolen

et al. 2023

Drugs

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“…This particular cell line was generously provided by Dr. S. Nomura from Tokyo University, Japan. A highly metastatic subline YTN16P was established through an in vivo selection method involving repeated intraperitoneal administration of the metastatic subline of YTN16 34 . Culturing of these cells was conducted in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS; Sigma, St. Louis, MO, USA), 50U/mL penicillin, 50 mg/mL streptomycin (Life Technologies, Grand Island, NY, USA), 2.5 µg/mL Plasmocin prophylactic (InvivoGen, San Diego, USA), and an additional 2 µM/mL L-Glutamine (G7513 200 mM; Sigma).…”

Section: Methodsmentioning

confidence: 99%

Vagus nerve signal has an inhibitory influence on the development of peritoneal metastasis in murine gastric cancer

Futoh,

Miyato,

Yamaguchi

et al. 2024

Sci Rep

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The vagus nerve is the only pathway for transmitting parasympathetic signals between the brain and thoracoabdominal organs, thereby exhibiting anti-inflammatory functions through the cholinergic anti-inflammatory pathway. Despite often being resected during lymph node dissection in upper gastrointestinal cancer surgery, the impact of vagotomy on postoperative outcomes in gastric cancer patients remains unclear. Sub-diaphragmatic vagotomy was performed on C57BL/6 mice. Three weeks later, syngeneic murine gastric cancer cell line YTN16P was injected into the peritoneal cavity, and the number of peritoneal metastases (PM) on the mesentery and omentum compared with control mice. The phenotypes of immune cells in peritoneal lavage and omental milky spots one day after tumor inoculation were analyzed using flow cytometry and immunohistochemistry. Intraperitoneal transfer of 3 × 105 YTN16P significantly increased the number of metastatic nodules on the mesentery in the vagotomy group compared to the control group. The omental metastasis grade was also significantly higher in the vagotomy group. Phenotypic analysis of immune cells in peritoneal lavage did not reveal significant differences after vagotomy. However, vagotomized mice exhibited a notable increase in milky spot area, with a higher presence of cytokeratin(+) tumor cells, F4/80(+) macrophages, and CD3(+) T cells. Vagus nerve signaling appears to regulate the immune response dynamics within milky spots against disseminated tumor cells and inhibits the development of PM. Preserving the vagus nerve may offer advantages in advanced gastric cancer surgery to reduce peritoneal recurrence.

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“…In research utilizing a newly produced highly metastatic clone of murine gastric cancer cells, YTN16P, it was shown that infusion of PD-1 mAb through the intravenous or intraperitoneal route lowered the rate of metastasis development on the mesenteric surface by 30–40% as a monotherapy [ 46 ]. Additionally, previous studies utilizing colon [ 40 , 47 ] or ovarian cancer cells [ 48 , 49 , 50 ] have shown that anti-PD-1 mAb may partially, but not fully, inhibit the development of PM in immunocompetent animals.…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Immunotherapy for Peritoneal Carcinomatosis: Challenges and Prospective Outcomes

Ornella

Badrinath²,

Kim³

et al. 2023

Cancers

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Peritoneal metastasis, also known as peritoneal carcinomatosis (PC), is a refractory cancer that is typically resistant to conventional therapies. The typical treatment for PC is a combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Recently, research in this area has seen significant advances, particularly in immunotherapy as an alternative therapy for PC, which is very encouraging. Catumaxomab is a trifunctional antibody intraperitoneal (IP) immunotherapy authorized in Europe that can be used to diminish malignant ascites by targeting EpCAM. Intraperitoneal (IP) immunotherapy breaks immunological tolerance to treat peritoneal illness. Increasing T-cell responses and vaccination against tumor-associated antigens are two methods of treatment. CAR-T cells, vaccine-based therapeutics, dendritic cells (DCs) in combination with pro-inflammatory cytokines and NKs, adoptive cell transfer, and immune checkpoint inhibitors are promising treatments for PC. Carcinoembryonic antigen-expressing tumors are suppressed by IP administration of CAR-T cells. This reaction was strengthened by anti-PD-L1 or anti-Gr1. When paired with CD137 co-stimulatory signaling, CAR-T cells for folate receptor cancers made it easier for T-cell tumors to find their way to and stay alive in the body.

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Effect of Systemic or Intraperitoneal Administration of Anti-PD-1 Antibody for Peritoneal Metastases from Gastric Cancer

Abstract: Background/Aim: Programmed death-1 (PD-

Cited by 13 publications

References 59 publications

Intraperitoneal Chemotherapy for Unresectable Peritoneal Surface Malignancies

Intraperitoneal Chemotherapy for Unresectable Peritoneal Surface Malignancies

Vagus nerve signal has an inhibitory influence on the development of peritoneal metastasis in murine gastric cancer

Immunotherapy for Peritoneal Carcinomatosis: Challenges and Prospective Outcomes

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