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Updated: Dec 21, 2025
An Orthotopic Resectional Mouse Model of Pancreatic Cancer
Published on: September 24, 2020
Targeting CA 19-9 with a humanized monoclonal antibody at the time of surgery may decrease recurrence rates for
Shreya Gupta1, James D McDonald1, Reed I Ayabe1
1Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Abstract:
Operable gastrointestinal cancers continue to pose significant challenges. Radical resections are rarely curative, and chemotherapy is able to reduce tumor recurrence for only a small percentage of patients. Despite the obvious advantages of extirpation of the identifiable tumor(s), the inflammatory milieu that accompanies surgery and the obligate time off cytotoxic agents allows for activation of remote quiescent disseminated tumor cells, leading to metastatic recurrence. We are conducting a study to determine the safety and efficacy of immediate peri-operative MVT-5873, a cytotoxic monoclonal antibody targeting carbohydrate antigen 19-9 (CA 19-9), in patients undergoing resections pancreatic cancer, cholangiocarcinoma or metastatic colorectal cancer to the liver. Eligible patients will receive a single dose of MVT-5873 three days before resection and four post-operative infusions, before beginning standard adjuvant regimens. MVT-5873 is a human IgG1 antibody isolated from a patient following immunization with a sLea-KLH vaccine. MVT-5873 demonstrated cell surface binding in sLea positive human tumor lines and has been shown to be potent in complement-dependent cytotoxicity assays and antibody-dependent cell mediated cytotoxicity assays. In patients with metastatic CA 19-9 producing pancreatic adenocarcinoma, MVT-5873 treatment has been shown to decrease serum CA 19-9 levels and prevent tumor progression. The use of perioperative MVT-5873 has the potential to reduce recurrence rates and prolong survival after resection. This trial may open the door for investigation of additional and/or synergistic agents in the immediate peri-operative period and usher in a new paradigm in the management of surgically treated cancers.
Trial Registration:
https://clinicaltrials.gov/ct2/show/NCT03801915?term=MVT&rank=3.
Insights
This study investigates MVT-5873, a novel antibody targeting CA 19-9, for gastrointestinal cancers. Perioperative administration aims to reduce tumor recurrence and improve survival after surgery.
Area of Science:
- Oncology
- Immunotherapy
- Gastrointestinal Cancers
Background:
- Gastrointestinal cancers pose significant challenges, with limited curative options post-resection.
- Surgical intervention can paradoxically promote metastatic recurrence by altering the inflammatory environment.
- Current adjuvant therapies offer limited efficacy in preventing tumor relapse.
Purpose of the Study:
- To evaluate the safety and efficacy of perioperative MVT-5873 in patients undergoing resection for pancreatic cancer, cholangiocarcinoma, or liver metastases from colorectal cancer.
- To assess the potential of MVT-5873 to mitigate tumor recurrence and enhance survival following surgical treatment.
Main Methods:
- A clinical trial administering MVT-5873, a monoclonal antibody targeting CA 19-9, perioperatively.
- Patients receive a single pre-operative dose and four post-operative infusions before standard adjuvant therapy.
- MVT-5873 is a human IgG1 antibody with demonstrated in vitro cytotoxicity.
Main Results:
- MVT-5873 exhibits cell surface binding to CA 19-9 positive tumor cells.
- The antibody is potent in complement-dependent and antibody-dependent cell-mediated cytotoxicity assays.
- Previous studies show MVT-5873 decreases serum CA 19-9 levels and prevents progression in pancreatic adenocarcinoma.
Conclusions:
- Perioperative MVT-5873 has the potential to reduce recurrence rates after surgical resection of gastrointestinal cancers.
- This approach may prolong patient survival and establish a new treatment paradigm.
- Further investigation into synergistic agents in the perioperative period is warranted.
