Contact Information

Primary Contact

Mitchell Ho, PhD
Senior Investigator


37 Convent Drive
BG 37 RM 5002
Bethesda, MD 20892


The Antibody Engineering Program (AEP) is part of the Center for Cancer Research (CCR) at the National Cancer Institute (NCI). The program focuses on generating therapeutic antibodies by phage display technology, including single domain antibodies (also known as ‘nanobodies’). While antibody-based therapeutics have emerged as a major component in clinical applications, the generation of antibodies to important targets such as cell surface receptors, ion channels, and glycoproteins remains challenging. Single domain antibodies have shown a promising ability to target difficult antigens and buried functional sites. Dr. Mitchell Ho and colleagues at the NCI have demonstrated that single domain antibodies are capable of targeting 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 libraries [Feng et al. 2019; Hong et al. 2022] and isolated binders to a wide range of antigens, indicating that the phage-displayed single domain antibody libraries can be a valuable source for drug discovery.

Using the single domain libraries created by the Ho lab, the AEP is interested in collaborating with intramural research and clinical laboratories to develop novel antibodies for difficult or unexplored targets in cancer, infectious diseases, and other human diseases. Interested collaborators should submit a proposal outlining the biological and clinical importance of their antigen and provide adequate background information for their proposal, including relevant antigen proteins (1-2 mg high-quality protein required), cell lines, animal models, and commercially available antibodies. This information will then be used for the AEP to evaluate and approve the project. The AEP will charge each project a $5000 flat fee to screen antibodies using up to two phage display libraries. The NCI/CCR may provide subsidies 50% of the fee for NCI intramural laboratories. At the end of each project, the AEP will provide phage or phagemids along with the final report including the DNA and amino acid sequences, CDR annotations, and the alignment of up to five closest sequences from GenBank for all the binders.


  • Feng M, Gao W, Wang R, Chen W, Man YG, Figg WD, Wang XW, Dimitrov DS, Ho M. Therapeutically targeting glypican-3 via a conformation-specific single-domain antibody in hepatocellular carcinoma. Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):E1083-91.
  • Gao W, Tang Z, Zhang YF, Feng M, Qian M, Dimitrov DS, Ho M. Immunotoxin targeting glypican-3 regresses liver cancer via dual inhibition of Wnt signaling and protein synthesis. Nat Commun. 2015 Mar 11;6:6536.
  • Li N, Fu H, Hewitt SM, Dimitrov DS, Ho M. Therapeutically targeting glypican-2 via single-domain antibody-based chimeric antigen receptors and immunotoxins in neuroblastoma. Proc Natl Acad Sci U S A. 2017 Aug 8;114(32):E6623-E6631. doi: 10.1073/pnas.1706055114. Epub 2017 Jul 24.
  • Hong J, Kwon HJ, Cachau R, Chen CZ, Butay KJ, Duan Z, Li D, Ren H, Liang T, Zhu J, Dandey VP, Martin NP, Esposito D, Ortega-Rodriguez U, Xu M, Borgnia MJ, Xie H, Ho M. Dromedary camel nanobodies broadly neutralize SARS-CoV-2 variants. Proc Natl Acad Sci U S A. 2022 May 3;119(18):e2201433119. doi: 10.1073/pnas.2201433119. Epub 2022 Apr 27.
  • Li N, Quan A, Li D, Pan J, Ren H, Hoeltzel G, de Val N, Ashworth D, Ni W, Zhou J, Mackay S, Hewitt SM, Cachau R, Ho M. The IgG4 hinge with CD28 transmembrane domain improves VHH-based CAR T cells targeting a membrane-distal epitope of GPC1 in pancreatic cancer. Nat Commun. 2023 Apr 8;14(1):1986. doi: 10.1038/s41467-023-37616-4.
  • Buffington J, Duan Z, Kwon HJ, Hong J, Li D, Feng M, Xie H, Ho M. Identification of nurse shark VNAR single-domain antibodies targeting the spike S2 subunit of SARS-CoV-2. FASEB J. 2023 Jun;37(6):e22973. doi: 10.1096/fj.202202099RR.
  • Feng M, Bian H, Wu X, Fu T, Fu Y, Hong J, Fleming BD, Flajnik MF, Ho M. Construction and next-generation sequencing analysis of a large phage-displayed VNAR single-domain antibody library from six naïve nurse sharks. Antib Ther. 2019 Jan;2(1):1-11.