Preventative Cancer Vaccine-Elicited Human Anti-MUC1 Antibodies Have Multiple Effector Functions
Background/Objectives: Mucin-1 (MUC1) is a transmembrane glycoprotein that is overexpressed and hypoglycosylated in premalignant and malignant epithelial cells compared to normal cells, creating a target antigen for humoral and cellular immunity. Healthy individuals with a history of advanced coloni...
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MDPI AG
2024-10-01
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| Online Access: | https://www.mdpi.com/2073-4468/13/4/85 |
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| author | Michelle L. McKeague Jason Lohmueller Matthew T. Dracz Najla Saadallah Eric D. Ricci Donella M. Beckwith Ramya Ayyalasomayajula Maré Cudic Olivera J. Finn |
| author_facet | Michelle L. McKeague Jason Lohmueller Matthew T. Dracz Najla Saadallah Eric D. Ricci Donella M. Beckwith Ramya Ayyalasomayajula Maré Cudic Olivera J. Finn |
| author_sort | Michelle L. McKeague |
| collection | DOAJ |
| description | Background/Objectives: Mucin-1 (MUC1) is a transmembrane glycoprotein that is overexpressed and hypoglycosylated in premalignant and malignant epithelial cells compared to normal cells, creating a target antigen for humoral and cellular immunity. Healthy individuals with a history of advanced colonic adenomas and at high risk for colon cancer were enrolled in a clinical trial to evaluate the feasibility of using a MUC1 peptide vaccine to prevent colon cancer. Anti-MUC1 antibodies elicited by this vaccine were cloned using peripheral blood B cells and sera collected two weeks after a one-year booster. Twelve of these fully human monoclonal antibodies (mAb) were tested for binding to MUC1+ target cells, and three with the highest binding were further evaluated for various effector functions important for tumor rejection. Methods: Immune cells were incubated together with target cells expressing variations in the number, distance, and membrane anchoring properties of the MUC1 epitope in the presence of each mAb. Results: All three mAbs mediated antibody-dependent cytokine release (ADCR), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). Two also mediated antibody-dependent trogocytosis/trogoptosis (ADCT). None were capable of complement-dependent cytotoxicity (CDC). Conclusions: ADCP and ADCT functions were more efficient when antibodies bound epitopes proximal to and anchored to the membrane, providing insight for future therapeutic antibody validation strategies. |
| format | Article |
| id | doaj-art-4fe0c2ac657244ad8b61ceb0ad2c2e33 |
| institution | Kabale University |
| issn | 2073-4468 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibodies |
| spelling | doaj-art-4fe0c2ac657244ad8b61ceb0ad2c2e332024-12-27T14:06:29ZengMDPI AGAntibodies2073-44682024-10-011348510.3390/antib13040085Preventative Cancer Vaccine-Elicited Human Anti-MUC1 Antibodies Have Multiple Effector FunctionsMichelle L. McKeague0Jason Lohmueller1Matthew T. Dracz2Najla Saadallah3Eric D. Ricci4Donella M. Beckwith5Ramya Ayyalasomayajula6Maré Cudic7Olivera J. Finn8Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Immunology, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Immunology, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Immunology, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Immunology, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431, USADepartment of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431, USADepartment of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL 33431, USADepartment of Immunology, University of Pittsburgh, Pittsburgh, PA 15213, USABackground/Objectives: Mucin-1 (MUC1) is a transmembrane glycoprotein that is overexpressed and hypoglycosylated in premalignant and malignant epithelial cells compared to normal cells, creating a target antigen for humoral and cellular immunity. Healthy individuals with a history of advanced colonic adenomas and at high risk for colon cancer were enrolled in a clinical trial to evaluate the feasibility of using a MUC1 peptide vaccine to prevent colon cancer. Anti-MUC1 antibodies elicited by this vaccine were cloned using peripheral blood B cells and sera collected two weeks after a one-year booster. Twelve of these fully human monoclonal antibodies (mAb) were tested for binding to MUC1+ target cells, and three with the highest binding were further evaluated for various effector functions important for tumor rejection. Methods: Immune cells were incubated together with target cells expressing variations in the number, distance, and membrane anchoring properties of the MUC1 epitope in the presence of each mAb. Results: All three mAbs mediated antibody-dependent cytokine release (ADCR), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). Two also mediated antibody-dependent trogocytosis/trogoptosis (ADCT). None were capable of complement-dependent cytotoxicity (CDC). Conclusions: ADCP and ADCT functions were more efficient when antibodies bound epitopes proximal to and anchored to the membrane, providing insight for future therapeutic antibody validation strategies.https://www.mdpi.com/2073-4468/13/4/85mucin-1phagocytosistrogocytosisNK cellmonocyteneutrophil |
| spellingShingle | Michelle L. McKeague Jason Lohmueller Matthew T. Dracz Najla Saadallah Eric D. Ricci Donella M. Beckwith Ramya Ayyalasomayajula Maré Cudic Olivera J. Finn Preventative Cancer Vaccine-Elicited Human Anti-MUC1 Antibodies Have Multiple Effector Functions Antibodies mucin-1 phagocytosis trogocytosis NK cell monocyte neutrophil |
| title | Preventative Cancer Vaccine-Elicited Human Anti-MUC1 Antibodies Have Multiple Effector Functions |
| title_full | Preventative Cancer Vaccine-Elicited Human Anti-MUC1 Antibodies Have Multiple Effector Functions |
| title_fullStr | Preventative Cancer Vaccine-Elicited Human Anti-MUC1 Antibodies Have Multiple Effector Functions |
| title_full_unstemmed | Preventative Cancer Vaccine-Elicited Human Anti-MUC1 Antibodies Have Multiple Effector Functions |
| title_short | Preventative Cancer Vaccine-Elicited Human Anti-MUC1 Antibodies Have Multiple Effector Functions |
| title_sort | preventative cancer vaccine elicited human anti muc1 antibodies have multiple effector functions |
| topic | mucin-1 phagocytosis trogocytosis NK cell monocyte neutrophil |
| url | https://www.mdpi.com/2073-4468/13/4/85 |
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