Addition of interleukin-12 to GA733 tumor protein vaccine leads to development of tumor protective immunity despite surgical stress

• Published in: Surgical endoscopy Vol. 17; no. 7; pp. 1135 - 1139
• Main Authors: KIRMAN, I, POLTORATSKAIA, N, HERLYN, D, WHELAN, R. L
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01.07.2003; Springer Nature B.V
• Subjects: Adjuvants, Immunologic - administration & dosage; Animals; Antibodies; Antigens; Antigens, Neoplasm - administration & dosage; Biological and medical sciences; Cancer therapies; Cancer Vaccines; Carbon dioxide; CD3 Complex - administration & dosage; Cell Adhesion Molecules - administration & dosage; Colorectal cancer; Cytokines; Epithelial Cell Adhesion Molecule; Female; Immunotherapy; Interleukin-12 - administration & dosage; Laparotomy; Medical sciences; Mice; Mice, Inbred BALB C; Neoplasms - etiology; Neoplasms - prevention & control; Proteins; Stress, Physiological - complications; Surgery; Surgical Procedures, Operative - adverse effects; Tumors; Vaccines; New York; United States > US; Vaccine; EpCAM; IL-12; Laparotomy; Antibody; Insufflation
• ISSN: 0930-2794; 1432-2218
• DOI: 10.1007/s00464-002-8744-7

We have previously shown that preoperative vaccination with the GA733 protein does not inhibit tumor growth in mice undergoing open surgery or carbon dioxide insufflation. In this study we assessed the antitumor effect of a combined GA733 and interleukin-12 (IL-12) vaccine. For this study, BALB/c mice were immunized with GA733, IL-12, or GA733 and IL-12, or they received no vaccine. Immediately after surgery (laparotomy or insufflation), GA733-transfected CT26 cells (C26-GA733) were injected subcutaneously into all mice. After 5 weeks, the mice were sacrificed, their tumors measured, GA733-specific antibodies determined by enzyme-linked immunoassay, and GA-733-specific cytotoxicity tested by flow cytometry using labeled C26-GA733 cells. Tumors were significantly (p < 0.05) smaller in both the insufflation and open groups that received combined GA733 and IL-12 than in their respective control subjects. Vaccination also induced a significant increase in the antibody and cell-mediated tumor-specific immunity. A preoperative vaccine consisting of GA733 and IL-12 inhibited postoperative tumor growth after open and closed surgery and allowed the mice to overcome the immunosuppressive effects of surgery.