NATIONAL CANCER INSTITUTE - CANCER.GOV

Contact Information

Primary Contact

Mitchell Ho, PhD
Senior Investigator

Location

37 Convent Drive
BG 37 RM 5046
Bethesda, MD 20892

Overview

The Antibody Engineering Program (AEP) is located at the Laboratory of Molecular Biology, which is part of the Center for Cancer Research (CCR), an intramural program at the National Cancer Institute (NCI). AEP focuses on generating therapeutic antibodies using phage display technology, including single-domain antibodies (also commonly known as ‘nanobodies’). Antibody-based therapeutics have emerged as a major component in clinical applications, and single-domain antibodies have shown promise in targeting difficult antigens and buried sites. Dr. Mitchell Ho and colleagues at the NCI have demonstrated that single-domain antibodies can target buried functional sites in cancer and viral antigens [Feng et al. 2013; Gao et al. 2015; Li et al. 2017; Hong et al. 2022; Li et al. 2023; Buffington et al. 2023]. His lab has constructed large shark and camel single-domain antibody libraries [Feng et al. 2019; Hong et al. 2022] and isolated binders to a wide range of antigens, demonstrating that phage-displayed single-domain antibody libraries can be a valuable source for drug discovery.

User Guidelines

Using the single-domain libraries created by the Ho lab, the AEP is collaborating with intramural research and clinical laboratories at the NCI to develop novel antibodies for challenging or unexplored targets in cancer and other human diseases. Interested collaborators should submit a proposal outlining the biological and clinical significance of their antigen and provide adequate background information, including relevant antigen proteins (1-2 mg of high-quality protein required), as well as details about cell lines, animal models, and commercially available antibodies. This information will be used by the AEP to evaluate and approve the project.

The AEP will charge a flat fee of $5,000 for each project to screen antibodies using two to three proprietary phage display libraries. The NCI/CCR may provide a 50% subsidy of the fee for NCI intramural laboratories. At the end of each project, the AEP will provide phage or phagemids, along with a final report that includes the DNA and amino acid sequences, CDR annotations, and the alignment of up to five closest sequences from GenBank for all the binders. If feasible, the AEP will also produce a small amount (>100 µg) of each nanobody for initial testing in the collaborator’s lab.

Publications

  • Duan Z, Li D, Li N, Lin S, Ren H, Hong J, Hinrichs CS, Ho M. CAR-T cells based on a TCR mimic nanobody targeting HPV16 E6 exhibit antitumor activity against cervical cancer. Mol Ther Oncol. 2024 Oct 9;32(4):200892. doi: 10.1016/j.omton.2024.200892.
  • Basuli F, Shi J, Lindberg E, Fayn S, Lee W, Ho M, Hammoud DA, Cheloha RW, Swenson RE, Escorcia FE. Sortase-Mediated Site-Specific Conjugation to Prepare Fluorine-18-Labeled Nanobodies. Bioconjug Chem. 2024 Sep 18;35(9):1335-1342. doi: 10.1021/acs.bioconjchem.4c00264. E
  • Gorman J, Cheung CS, Duan Z, Ou L, Wang M, Chen X, Cheng C, Biju A, Sun Y, Wang P, Yang Y, Zhang B, Boyington JC, Bylund T, Charaf S, Chen SJ, Du H, Henry AR, Liu T, Sarfo EK, Schramm CA, Shen CH, Stephens T, Teng IT, Todd JP, Tsybovsky Y, Verardi R, Wang D, Wang S, Wang Z, Zheng CY, Zhou T, Douek DC, Mascola JR, Ho DD, Ho M, Kwong PD. Share Cleavage-intermediate Lassa virus trimer elicits neutralizing responses, identifies neutralizing nanobodies, and reveals an apex-situated site-of-vulnerability. Nat Commun. 2024 Jan 4;15(1):285. doi: 10.1038/s41467-023-44534-y.
  • Li D, Wang R, Liang T, Ren H, Park C, Tai CH, Ni W, Zhou J, Mackay S, Edmondson E, Khan J, Croix BS, Ho M. Share Camel nanobody-based B7-H3 CAR-T cells show high efficacy against large solid tumours. Nat Commun. 2023 Sep 22;14(1):5920. doi: 10.1038/s41467-023-41631-w.
  • Fayn S, King AP, Gutsche NT, Duan Z, Buffington J, Olkowski CP, Fu Y, Hong J, Sail D, Baidoo KE, Swenson RE, Cheloha RW, Ho M, Choyke PL, Escorcia FE. Share Site-Specifically Conjugated Single-Domain Antibody Successfully Identifies Glypican-3-Expressing Liver Cancer by Immuno-PET. J Nucl Med. 2023 Jul;64(7):1017-1023. doi: 10.2967/jnumed.122.265171.

Keywords

Antibody sequence analysisCamel single domain antibodiesHuman antibodiesIgNanobodiesPhage displayProtein EngineeringShark single domain antibodiesSingle domain antibodiesababsantibodiesantibodyantibody engineeringimmunoglobulinmonoclonal antibodiesVHHVNARscFvFv