Journal
ANNALS OF SURGICAL ONCOLOGY
Volume 21, Issue 12, Pages 3931-3937Publisher
SPRINGER
DOI: 10.1245/s10434-014-3844-x
Keywords
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Funding
- NIH [K23 CA 104160-05, R01 CA112160, K23 CA148964]
- Johns Hopkins University School of Medicine Clinician Scientist Award
- Lefkofsky Family Foundation
- NCI SPORE in Gastrointestinal Cancers [P50 CA062924]
- Zhang Family Gift Fund/Susan Cohan Colon Cancer Foundation
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Despite recent advances in earlier detection and improvements in chemotherapy, the 5-year survival rate of patients with metastatic colorectal carcinoma remains poor. Immunotherapy is a potentially effective therapeutic approach to the treatment of colorectal carcinoma. Preclinical studies have supported the antitumor activity of immunization with a granulocyte-macrophage colony-stimulating factor (GM-CSF) producing murine colon tumor cell vaccine. A novel colorectal cancer vaccine composed of irradiated, allogeneic human colon cancer cells and GM-CSF-producing bystander cells was developed and tested in combination with a single intravenous low dose of cyclophosphamide in a phase 1 study of patients with metastatic colorectal cancer. A total of nine patients were enrolled onto and treated in this study. Six patients had a history of colorectal adenocarcinoma hepatic metastases and underwent curative metastasectomy, while three other patients had unresectable stage IV disease. This study demonstrates the safety and feasibility of this vaccine administered in patients with metastatic colorectal cancer. At last follow-up, the six patients who underwent curative metastasectomy survived longer than 36 months, and four of these six patients were without disease recurrence. Immunologic correlate results suggest that the GM-CSF-producing colon cancer vaccine enhances the production of anti-MUC1 antibodies. This vaccine is feasible and safe. Future investigation of the efficacy and antitumor immunity of this vaccine is warranted.
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