Self-antigen MASH2 combined with the AS15 immunostimulant induces tumor protection in colorectal cancer mouse models
| Autor: | Hossein Koohsari, Harry S. Cooper, Laura Workman, Jean Michaud, Catherine Gérard, Esther Kaunga, Clément R. Rioux, Anthony Pilorget, Harvey Hensley, Natalie St Amant, Margie L. Clapper |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Colorectal cancer medicine.medical_treatment Cancer Treatment Apoptosis Autoantigens Mice White Blood Cells 0302 clinical medicine Cancer immunotherapy Animal Cells Basic Helix-Loop-Helix Transcription Factors Tumor Cells Cultured Medicine and Health Sciences Public and Occupational Health Multidisciplinary biology T Cells Immunogenicity Animal Models Adenomas Recombinant Proteins 3. Good health Oncology Experimental Organism Systems 030220 oncology & carcinogenesis Medicine Drug Therapy Combination Female Immunotherapy Anatomy Cellular Types Antibody Colorectal Neoplasms Research Article Genes APC Colon medicine.drug_class Immune Cells Science Immunology Mouse Models Research and Analysis Methods Cancer Vaccines Immunostimulant Cancer Immunotherapy 03 medical and health sciences Model Organisms Adjuvants Immunologic Antigen medicine Animals Humans Cell Proliferation Colorectal Cancer Blood Cells Prophylaxis business.industry Cancers and Neoplasms Biology and Life Sciences Cell Biology medicine.disease Gastrointestinal Tract Disease Models Animal 030104 developmental biology Animal Studies Cancer research biology.protein Clinical Immunology Preventive Medicine Clinical Medicine business Digestive System |
| Zdroj: | PLoS ONE, Vol 14, Iss 1, p e0210261 (2019) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Human achaete scute homolog 2 (HASH2) and its murine ortholog MASH2 are potential targets for colorectal cancer immunotherapy. We assessed immunogenicity and antitumor potential of recombinant MASH2 protein combined with AS15 immunostimulant (recMASH2+AS15) in CB6F1 and Apc+/Min-FCCC mice. CB6F1 mice received 4 injections of recMASH2+AS15 or AS15 alone before challenge with TC1-MASH2 tumor cells (Tumor Challenge). Apc+/Min-FCCC mice received 9 injections of recMASH2+AS15 or vehicle (phosphate buffer saline [PBS] or AS15 alone), before (two independent Prophylactic Studies) or after (Immunotherapy) colon adenomas were detectable by colonoscopy. CB6F1 mice immunized with recMASH2+AS15 had a significantly smaller mean tumor size and improved survival rate compared to controls (104 mm2 vs. 197 mm2 [p = 0.009] and 67% vs. 7% [p = 0.001], respectively). In Prophylactic Study 1, the mean number of colon adenomas was significantly lower in Apc+/Min-FCCC mice receiving recMASH2+AS15 compared to PBS (1.8 [95% confidence interval 1.0–3.3] vs. 5.2 [3.7–7.4], p = 0.003). Fewer microadenomas were observed in recMASH2+AS15 groups compared to PBS in both Prophylactic Studies (Study 1: mean 0.4 [0.2–1.0] vs. 1.5 [0.9–2.4], p = 0.009; Study 2: 0.4 [0.2–0.6] vs. 1.1 [0.8–1.5], p = 0.001). In the Immunotherapy Study, fewer colon adenomas tended to be observed in recMASH2+AS15-treated mice (4.1 [2.9–6.0]) compared to controls (AS15 4.7 [3.3–6.6]; PBS 4.9 [3.5–6.9]; no significant difference). recMASH2+AS15 induced MASH2-specific antibody and CD4+ responses in both mouse models. recMASH2+AS15 partially protected mice against MASH2-expressing tumors and reduced spontaneous colorectal adenomas in Apc+/Min-FCCC mice, indicating that MASH2/HASH2 antigens are targets for colorectal cancer immunotherapy. |
| Databáze: | OpenAIRE |
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