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A Novel In Vitro Wound Healing Assay to Evaluate Cell Migration
Published on: March 17, 2018
Effect of surgical trauma on epithelial cell adhesion molecule (GA-733) vaccine-induced tumor resistance
1Department of Surgery, College of Physicians and Surgeons of Columbia University, BB1716, 630 West 168th Street, New York, NY 10032, USA. ik139@columbia.edu
Background:
Surgical trauma inhibits immune function. Our goal was to study the effect of surgical intervention on the development of the immune response to epithelial cell adhesion molecule (EpCAM [GA-733]), a tumor-associated protein used for vaccination in colon cancer.
Methods:
Recombinant GA-733 and monophosphoryl-lipid A (MPLA) were incorporated into biodegradable beads and implanted in the following groups of mice: control, insufflation, and laparotomy. After surgery, the mice were inoculated with GA-733-transfected C26 cells (C26-EpCAM). Plasma anti-GA733 IgG antibodies were detected in enzyme-linked immunoassay (ELISA). Killing specific to GA-733 was assayed by C26-EpCAM-killing assay.
Results:
The difference in tumor size between immunized and nonimmunized animals was statistically significant only in control mice (p < 0.05). Greater cytotoxic response to C26-GA733 developed in all immunized mice groups than in their respective controls. However, anti-GA733 IgG increased significantly in the control and insufflation groups, but not in the laparotomy group.
Conclusions:
Combined GA-733 vaccine allows reduction of tumor growth in control but not in surgically managed animals. This vaccine can induce a specific-cell and antibody-mediated immune response. Open surgery leads to a decreased antibody response to the GA-733 tumor vaccine.
Insights
Surgical intervention impairs the immune response to the epithelial cell adhesion molecule (EpCAM) vaccine in colon cancer models. Open surgery significantly reduced antibody production, hindering vaccine efficacy against tumors.
Area of Science:
- Immunology
- Surgical Oncology
- Vaccine Development
Background:
- Surgical trauma is known to suppress immune function.
- The study investigates the impact of surgery on immune response to epithelial cell adhesion molecule (EpCAM), a target for colon cancer vaccination.
Purpose of the Study:
- To evaluate the effect of surgical intervention on the immune response to an EpCAM-based vaccine.
- To determine if surgical methods influence the efficacy of EpCAM vaccination in colon cancer.
Main Methods:
- Mice received a GA-733 (EpCAM) vaccine with monophosphoryl-lipid A (MPLA) via biodegradable beads.
- Surgical groups included control, insufflation, and laparotomy.
- Immune response was assessed by measuring anti-GA733 IgG antibodies and cytotoxic T-cell activity against EpCAM-expressing colon cancer cells.
Main Results:
- The GA-733 vaccine reduced tumor size significantly only in control mice.
- While all immunized groups showed a greater cytotoxic response than controls, anti-GA733 IgG levels increased significantly only in control and insufflation groups.
- Laparotomy surgery led to a significant decrease in antibody response to the EpCAM vaccine.
Conclusions:
- The GA-733 vaccine can reduce tumor growth and elicit specific immune responses.
- Open surgery (laparotomy) diminishes the antibody-mediated immune response to the EpCAM vaccine.
- Surgical management may compromise the effectiveness of EpCAM-targeted cancer vaccines.
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