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- Title
Human colorectal cancer antigen GA733-2-Fc fused to endoplasmic reticulum retention motif KDEL enhances its immunotherapeutic effects.
- Authors
Yuan-Yuan Fu; Jin Zhao; Jong-Hwa Park; Geun-Won Choi; Kong Young Park; Youn Hyung Lee; In Sik Chung; Fu, Yuan-Yuan; Zhao, Jin; Park, Jong-Hwa; Choi, Geun-Won; Park, Kong Young; Lee, Youn Hyung; Chung, In Sik
- Abstract
<bold>Objective: </bold>The aim of this is to compare the immunotherapeutic effects of human colorectal cancer antigen GA733-2 fused to the Fc fragment of antibody (GA733-2-Fc) and to Fc and endoplasmic reticulum (ER) retention motif KDEL (GA733-2-Fc-KDEL).<bold>Materials and Methods: </bold>Recombinant GA733-2-Fc and GA733-2-Fc-KDEL were produced from infiltrated Nicotiana benthamiana leaves and purified by affinity chromatography. Glycan structures were determined by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. The allergic and immunogenic responses of recombinant GA733-2-Fc and GA733-2-Fc-KDEL were estimated in an intraperitoneally immunized mouse. The tumor regression effect of recombinant GA733-2-Fc and GA733-2-Fc-KDEL was examined using a colorectal carcinoma CT-26 animal model.<bold>Results: </bold>Recombinant GA733-2-Fc contained plant-specific glycan structures including β(1,2)-xylose and α(1,3)-fucose whereas recombinant GA733-2-Fc-KDEL contained oligomannose type glycan structures. Mice immunized intraperitoneally with recombinant GA733-2-Fc and GA733-2-Fc-KDEL elicited strong GA733-2-Fc-specific immunoglobulin G (IgG) and IgA serum antibody responses. Recombinant GA733-2-Fc-KDEL reduced the production of GA733-2-Fc-specific IgE. Recombinant GA733-2-Fc-KDEL increased the production of interferon-γ. Intraperitoneal preimmunization with recombinant GA733-2-Fc and GA733-2-Fc-KDEL regressed tumor growth in a colorectal carcinoma CT-26 animal model. The tumor regression effect induced by recombinant GA733-2-Fc-KDEL was greater than that induced by recombinant GA733-2-Fc. The human and mouse colorectal carcinoma cell binding activities of recombinant GA733-2-Fc-KDEL-immunized sera were higher than those of recombinant GA733-2-Fc.<bold>Conclusions: </bold>Our results suggest that GA733-2-Fc conjugated to ER-retention motif KDEL is a more efficient antigen to prevent tumor growth induced by colorectal carcinoma and minimize an allergic response.
- Subjects
COLON cancer; ANTIGENS; ENDOPLASMIC reticulum; IMMUNE response; IMMUNOGLOBULINS
- Publication
Journal of Cancer Research & Therapeutics, 2018, Vol 14, pS748
- ISSN
0973-1482
- Publication type
journal article
- DOI
10.4103/0973-1482.199445