A tumor-binding antibody with cross-reactivity to viral antigens
Abstract Background We previously identified in non-small cell lung cancer (NSCLC) patients an autoantibody to complement factor H (CFH) that is associated with non-metastatic disease and longer time to progression in patients with stage I disease. A recombinant human antibody, GT103, was cloned fro...
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| Language: | English |
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Springer
2025-02-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-025-03975-8 |
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| author | Michael J. Campa Elizabeth B. Gottlin Kevin Wiehe Edward F. Patz |
| author_facet | Michael J. Campa Elizabeth B. Gottlin Kevin Wiehe Edward F. Patz |
| author_sort | Michael J. Campa |
| collection | DOAJ |
| description | Abstract Background We previously identified in non-small cell lung cancer (NSCLC) patients an autoantibody to complement factor H (CFH) that is associated with non-metastatic disease and longer time to progression in patients with stage I disease. A recombinant human antibody, GT103, was cloned from single B cells isolated from patients with the autoantibody. GT103 inhibits tumor growth and establishes an antitumor microenvironment. The anti-CFH autoantibody and GT103 recognize the epitope PIDNGDIT within the SCR19 domain of CFH. Here, we asked if this autoantibody could have originally arisen as a humoral response to a similar epitope in a viral protein from a prior infection. Methods Homologous viral peptides with high sequence identity to the core PIDNGDIT epitope sequence were identified and synthesized. NSCLC patient plasma containing anti-CFH autoantibodies were assayed by ELISA against these peptides. GT103 was assayed on a 4345-peptide pathogen microarray. Results Epitopes similar to the GT103 epitope are present in several viruses, including human metapneumovirus-1 (HMPV-1) that contains a sequence within attachment glycoprotein G that differs by one amino acid. Anti-CFH autoantibodies in NSCLC patient plasma weakly bound to an HMPV-1 peptide containing the epitope. GT103 cross-reacted with multiple viral epitopes on a peptide microarray, with the top hits being peptides in the human endogenous retrovirus-K polymerase (HERV-K pol) protein and measles hemagglutinin glycoprotein. GT103 bound the viral HMPV-1, HERV-K pol, and measles epitope peptides but with lower affinity compared to the GT103 epitope peptide. Conclusion These findings suggest that memory B cells against a viral target could have affinity matured to produce an antibody that recognizes a similar epitope on tumor cells and exhibits antitumor properties. |
| format | Article |
| id | doaj-art-fbb44b71099347b3b5c3bcc1e9a33c99 |
| institution | DOAJ |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-fbb44b71099347b3b5c3bcc1e9a33c992025-08-20T02:49:35ZengSpringerCancer Immunology, Immunotherapy1432-08512025-02-017441610.1007/s00262-025-03975-8A tumor-binding antibody with cross-reactivity to viral antigensMichael J. Campa0Elizabeth B. Gottlin1Kevin Wiehe2Edward F. Patz3Department of Radiology, Duke University School of MedicineDepartment of Radiology, Duke University School of MedicineDuke Human Vaccine Institute, Duke University School of MedicineDepartment of Radiology, Duke University School of MedicineAbstract Background We previously identified in non-small cell lung cancer (NSCLC) patients an autoantibody to complement factor H (CFH) that is associated with non-metastatic disease and longer time to progression in patients with stage I disease. A recombinant human antibody, GT103, was cloned from single B cells isolated from patients with the autoantibody. GT103 inhibits tumor growth and establishes an antitumor microenvironment. The anti-CFH autoantibody and GT103 recognize the epitope PIDNGDIT within the SCR19 domain of CFH. Here, we asked if this autoantibody could have originally arisen as a humoral response to a similar epitope in a viral protein from a prior infection. Methods Homologous viral peptides with high sequence identity to the core PIDNGDIT epitope sequence were identified and synthesized. NSCLC patient plasma containing anti-CFH autoantibodies were assayed by ELISA against these peptides. GT103 was assayed on a 4345-peptide pathogen microarray. Results Epitopes similar to the GT103 epitope are present in several viruses, including human metapneumovirus-1 (HMPV-1) that contains a sequence within attachment glycoprotein G that differs by one amino acid. Anti-CFH autoantibodies in NSCLC patient plasma weakly bound to an HMPV-1 peptide containing the epitope. GT103 cross-reacted with multiple viral epitopes on a peptide microarray, with the top hits being peptides in the human endogenous retrovirus-K polymerase (HERV-K pol) protein and measles hemagglutinin glycoprotein. GT103 bound the viral HMPV-1, HERV-K pol, and measles epitope peptides but with lower affinity compared to the GT103 epitope peptide. Conclusion These findings suggest that memory B cells against a viral target could have affinity matured to produce an antibody that recognizes a similar epitope on tumor cells and exhibits antitumor properties.https://doi.org/10.1007/s00262-025-03975-8AutoantibodiesViral epitopesAntibody cross-reactivityMolecular mimicryHumoral immunity |
| spellingShingle | Michael J. Campa Elizabeth B. Gottlin Kevin Wiehe Edward F. Patz A tumor-binding antibody with cross-reactivity to viral antigens Cancer Immunology, Immunotherapy Autoantibodies Viral epitopes Antibody cross-reactivity Molecular mimicry Humoral immunity |
| title | A tumor-binding antibody with cross-reactivity to viral antigens |
| title_full | A tumor-binding antibody with cross-reactivity to viral antigens |
| title_fullStr | A tumor-binding antibody with cross-reactivity to viral antigens |
| title_full_unstemmed | A tumor-binding antibody with cross-reactivity to viral antigens |
| title_short | A tumor-binding antibody with cross-reactivity to viral antigens |
| title_sort | tumor binding antibody with cross reactivity to viral antigens |
| topic | Autoantibodies Viral epitopes Antibody cross-reactivity Molecular mimicry Humoral immunity |
| url | https://doi.org/10.1007/s00262-025-03975-8 |
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