PUBLICATION
Antibody-peptide epitope conjugates for personalized cancer therapy
- Authors
- Zhang, S., Yan, C., Millar, D.G., Yang, Q., Heather, J.M., Langenbucher, A., Morton, L.T., Sepulveda, S., Alpert, E., Whelton, L.R., Zarrella, D.T., Guo, M., Minogue, E., Lawrence, M.S., Rueda, B.R., Spriggs, D.R., Lu, W., Langenau, D.M., Cobbold, M.
- ID
- ZDB-PUB-211231-2
- Date
- 2021
- Source
- Cancer research 82(5): 773-784 (Journal)
- Registered Authors
- Langenau, David
- Keywords
- none
- MeSH Terms
-
- Animals
- Antibodies
- CD8-Positive T-Lymphocytes
- Carcinoma, Ovarian Epithelial/drug therapy
- Cytomegalovirus
- Cytomegalovirus Infections*
- Epithelial Cell Adhesion Molecule
- Epitopes
- Female
- Humans
- Immunoconjugates*/therapeutic use
- Mice
- Ovarian Neoplasms*/drug therapy
- Peptide Hydrolases
- Peptides
- Zebrafish
- PubMed
- 34965933 Full text @ Cancer Res.
Citation
Zhang, S., Yan, C., Millar, D.G., Yang, Q., Heather, J.M., Langenbucher, A., Morton, L.T., Sepulveda, S., Alpert, E., Whelton, L.R., Zarrella, D.T., Guo, M., Minogue, E., Lawrence, M.S., Rueda, B.R., Spriggs, D.R., Lu, W., Langenau, D.M., Cobbold, M. (2021) Antibody-peptide epitope conjugates for personalized cancer therapy. Cancer research. 82(5):773-784.
Abstract
Antibody-peptide epitope conjugates (APEC) are a new class of modified antibody-drug conjugates that redirect T cell viral immunity against tumor cells. APECs contain a tumor-specific protease cleavage site linked to a patient-specific viral epitope, resulting in presentation of viral epitopes on cancer cells and subsequent recruitment and killing by CD8+ T cells. Here we developed an experimental pipeline to create patient-specific APECs and identified new preclinical therapies for ovarian carcinoma. Using functional assessment of viral peptide antigen responses to common viruses like cytomegalovirus (CMV) in ovarian cancer patients, a library of 192 APECs with distinct protease cleavage sequences was created using the anti-epithelial cell adhesion molecule (EpCAM) antibody. Each APEC was tested for in vitro cancer cell killing, and top candidates were screened for killing xenograft tumors grown in zebrafish and mice. These preclinical modeling studies identified EpCAM-MMP7-CMV APEC (EpCAM-MC) as a potential new immunotherapy for ovarian carcinoma. Importantly, EpCAM-MC also demonstrated robust T cell responses in primary ovarian carcinoma patient ascites samples. This work highlights a robust, customizable platform to rapidly develop patient-specific APECs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping