Combined whole tumor cell and monophosphoryl lipid A vaccine improved by encapsulation in murine colorectal cancer.
BACKGROUND
Whole autologous colon cancer vaccines in combination with various adjuvants have been used in both animals and humans. At this writing, vaccine regimens have been initiated in humans 3 to 6 weeks postoperatively. This delay between tumor resection and vaccination gives surviving tumor cells an opportunity to establish themselves. Vaccine administered either preoperatively or immediately after surgery, in theory, should be more effective. However, surgery-related immunosuppression may diminish the effectiveness of pre-operative or early postoperative vaccines. This problem may be overcome by limiting postoperative immunosuppression via the use of minimally invasive methods. Alternatively, the impact of the vaccine may be improved by encapsulating the vaccine, plus adjuvant, which in theory, should extend exposure time. Encapsulation of cancer vaccines in polysaccharide particles has not yet been studied. The goal of this study was to determine whether vaccine encapsulation, preoperative vaccination, and early postoperative vaccination affected the tumor burden. In addition, laparotomy and carbon dioxide insufflation were compared.


METHODS
Vaccine was prepared from ultraviolet-irradiated C26 colon cancer cells in combination with monophosphoryl lipid A, either in suspension or entrapped in alginate beads. The C26 cell line and syngeneic BALB/c mice were used for all the studies. Tumor volumes were determined after excision of the tumors 2 weeks after inoculation in these studies.


RESULTS
Encapsulated vaccine was more effective than the standard liquid vaccine. Significantly smaller tumors were noted in mice receiving encapsulated vaccine than in either the control group (p <0.01) or the liquid vaccine group (p <0.05). The use of a preoperative encapsulated vaccine was associated with significantly smaller tumors after laparotomy, pneumoperitoneum, or anesthesia alone when the tumors were established immediately after surgery. With an already established tumor, encapsulated vaccine, when given in the early postoperative period to mice that had undergone laparotomy or anesthesia alone was associated with significantly smaller tumors that those found in control animals.


CONCLUSIONS
The incorporation of a whole-cell vaccine and monophosphoryl lipid A into alginate beads increases the efficacy of pre-operative and early postoperative tumor vaccines in the setting of both laparotomy and Carbon dioxide pneumoperitoneum. The use of perioperative vaccines may prove to be an effective way to immunize patients with cancer undergoing surgery.
Kirman
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I
Department of Surgery, College of Physicians and Surgeons of Columbia University, 630 W. 168th Street, New York, 10032, USA. ik139@columbia.edu
Asi
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Carter
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Fowler
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Whelan
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RL
D000230:Adenocarcinoma / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000464:Alginates / Q000627:therapeutic use; D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002214:Capsules / Q000627:therapeutic use; D002245:Carbon Dioxide / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D015179:Colorectal Neoplasms / Q000473:pathology*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D007327:Insufflation / Q000379:methods; D007813:Laparotomy / Q000379:methods; D008050:Lipid A / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009368:Neoplasm Transplantation / Q000379:methods*; D011134:Polysaccharides / Q000627:therapeutic use; D011182:Postoperative Care / Q000379:methods; D011300:Preoperative Care / Q000379:methods; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000464:Alginates; D019496:Cancer Vaccines; D002214:Capsules; D006603:Hexuronic Acids; D008050:Lipid A; D011134:Polysaccharides; D002245:Carbon Dioxide; D020723:Glucuronic Acid; C048436:monophosphoryl lipid A