Mitchell  Ho, Ph.D.
Mitchell Ho, Ph.D.
Investigator
Head, Antibody Therapy Section

Center for Cancer Research
National Cancer Institute

Building 37, Room 5002C
Bethesda, MD 20892-4264
301-451-8727

Dr. Ho uses antibody engineering to generate novel antibodies for cancer treatment. He has two main research areas. The first focuses on glypican 3. His group has developed new antibodies to glypican 3 that inactivate cancer signaling and inhibit liver tumor growth. The second area focuses on mesothelin. Along with his collaborators, Dr. Ho has identified new antibodies that recognize unique epitopes in mesothelin for the treatment and diagnostics of mesothelioma and other cancers.

Dr. Ho also serves as Chair of the NIH Antibody Interest Group, and he is Co-Chair of the Department of Biochemistry in the FAES Graduate School at the NIH.

Areas of Expertise
1) antibody engineering, 2) human monoclonal antibodies, 3) heavy-chain antibodies

Development of New Antibody-Based Cancer Therapies

Research in the Ho lab is focused on the application of antibody engineering for the development of cancer therapeutics. In particular, we have generated novel antibodies targeting glypican-3 (GPC3) and mesothelin for the treatment of liver cancer, mesothelioma and other cancers.

GPC3 is highly expressed in hepatocellular carcinoma (HCC) and other cancers. We have generated high-affinity antibodies targeting GPC3, including YP7 – an antibody that recognizes a C-terminal site (511-560) in GPC3. Furthermore, we generated two human antibodies (HN3 and HS20). HN3 is a heavy-chain antibody that recognizes the core protein of GPC3 and inhibits proliferation of HCC cells. The underlying mechanism of HN3 action may involve inhibition of Yap signaling in liver cancer cells. HS20 preferentially recognizes the heparan sulfate chains of GPC3 and inhibits Wnt signaling. The new antibodies exhibit significant inhibition of liver tumor growth in mice and show potential for use as therapeutic candidates.

Mesothelin is expressed in mesothelioma, ovarian cancer,  pancreatic cancer, lung cancer, breast cancer, cholangiocarcinoma and other cancers. The molecular interaction between mesothelin  and MUC16 (also known as CA125) may facilitate the implantation and spread of tumors. We identified the functional binding domain  (named IAB, 296-359) in mesothelin for MUC16. We generated two human antibodies specific for mesothelin. The HN1 human antibody disrupts the mesothelin-MUC16 interaction and elicits antibody‐dependent cell-mediated cytotoxicity (ADCC) against tumor cells. SD1 is a human heavy-chain antibody that recognizes a unique site (539-588) in mesothelin close to the cell surface and exhibits complement-dependent cytotoxicity (CDC) as well as  ADCC against tumor cells. The new antibodies show potential for the treatment and diagnostics of cancers.

Teaching Interests:  BIOC301/302 - Biochemistry I/II

Scientific Focus Areas:
Cell Biology, Molecular Biology and Biochemistry

View Dr. Ho's PubMed Summary.

Selected Recent Publications
  1. Phung Y, Gao W, Man YG, Nagata S, Ho M.
    MAbs. 4: 592-9, 2012. [ Journal Article ]
  2. Tang Z, Feng M, Gao W, Phung Y, Chen W, Chaudhary A, St Croix B, Qian M, Dimitrov DS, Ho M.
    Mol. Cancer Ther. 12: 416-26, 2013. [ Journal Article ]
  3. Feng M, Gao W, Wang R, Chen W, Man YG, Figg WD, Wang XW, Dimitrov DS, Ho M.
    Proc. Natl. Acad. Sci. U.S.A. 110: E1083-91, 2013. [ Journal Article ]
  4. Gao W, Kim H, Feng M, Phung Y, Xavier CP, Rubin JS, Ho M.
    Hepatology. 60: 576-87, 2014. [ Journal Article ]
  5. Gao W, Tang Z, Zhang YF, Feng M, Qian M, Dimitrov DS, Ho M.
    Nat Commun. 6: 6536, 2015. [ Journal Article ]

Dr. Mitchell Ho is Chief of the Antibody Therapy Section, Laboratory of Molecular Biology, in the NCI. Dr. Ho received his Ph.D. from the University of Illinois at Urbana-Champaign under Mariangela Segre. He won a National Research Service Award Predoctoral Fellowship from the National Institute on Drug Abuse (NIDA) for his Ph.D. thesis research on the generation of monoclonal antibodies against cocaine addiction. He was a postdoctoral fellow under Ira Pastan at the NCI and generated immunotoxins against cancer.

Dr. Ho is a recipient of the NCI Director's Intramural Innovation Award for Principal Investigators, the Mesothelioma Applied Research Foundation Grant Award, the Ovarian Cancer Research Fund Individual Investigator Award and the NIH Merit Award. He is Chair of the NIH Antibody Interest Group, and serves on the Antibody Society's Board of Distinguished Advisors. Dr. Ho regularly presents at international symposia and is a member of the organizing committees for several international conferences on therapeutic antibodies. He is Co-Chair of the Department of Biochemistry in the FAES Graduate School at the NIH. He is also a Distinguished Zijiang Visiting Chair Professor at East China Normal University.

Name Position
Mingqian Feng Ph.D. Research Fellow
Wei Gao Ph.D. Postdoctoral Fellow (Visiting)
Sophia Gauthier Summer Student
Hannah Jacobs Summer Student
Nan Li Ph.D. Postdoctoral Fellow (Visiting)
Min Ni M.D. Special Volunteer
Chunguang Wang M.D. Special Volunteer
Yifan Zhang Ph.D. Postdoctoral Fellow (Visiting)

Summary

Dr. Ho uses antibody engineering to generate novel antibodies for cancer treatment. He has two main research areas. The first focuses on glypican 3. His group has developed new antibodies to glypican 3 that inactivate cancer signaling and inhibit liver tumor growth. The second area focuses on mesothelin. Along with his collaborators, Dr. Ho has identified new antibodies that recognize unique epitopes in mesothelin for the treatment and diagnostics of mesothelioma and other cancers.

Dr. Ho also serves as Chair of the NIH Antibody Interest Group, and he is Co-Chair of the Department of Biochemistry in the FAES Graduate School at the NIH.

Areas of Expertise
1) antibody engineering, 2) human monoclonal antibodies, 3) heavy-chain antibodies

Research

Development of New Antibody-Based Cancer Therapies

Research in the Ho lab is focused on the application of antibody engineering for the development of cancer therapeutics. In particular, we have generated novel antibodies targeting glypican-3 (GPC3) and mesothelin for the treatment of liver cancer, mesothelioma and other cancers.

GPC3 is highly expressed in hepatocellular carcinoma (HCC) and other cancers. We have generated high-affinity antibodies targeting GPC3, including YP7 – an antibody that recognizes a C-terminal site (511-560) in GPC3. Furthermore, we generated two human antibodies (HN3 and HS20). HN3 is a heavy-chain antibody that recognizes the core protein of GPC3 and inhibits proliferation of HCC cells. The underlying mechanism of HN3 action may involve inhibition of Yap signaling in liver cancer cells. HS20 preferentially recognizes the heparan sulfate chains of GPC3 and inhibits Wnt signaling. The new antibodies exhibit significant inhibition of liver tumor growth in mice and show potential for use as therapeutic candidates.

Mesothelin is expressed in mesothelioma, ovarian cancer,  pancreatic cancer, lung cancer, breast cancer, cholangiocarcinoma and other cancers. The molecular interaction between mesothelin  and MUC16 (also known as CA125) may facilitate the implantation and spread of tumors. We identified the functional binding domain  (named IAB, 296-359) in mesothelin for MUC16. We generated two human antibodies specific for mesothelin. The HN1 human antibody disrupts the mesothelin-MUC16 interaction and elicits antibody‐dependent cell-mediated cytotoxicity (ADCC) against tumor cells. SD1 is a human heavy-chain antibody that recognizes a unique site (539-588) in mesothelin close to the cell surface and exhibits complement-dependent cytotoxicity (CDC) as well as  ADCC against tumor cells. The new antibodies show potential for the treatment and diagnostics of cancers.

Teaching Interests:  BIOC301/302 - Biochemistry I/II

Scientific Focus Areas:
Cell Biology, Molecular Biology and Biochemistry

Publications

View Dr. Ho's PubMed Summary.

Selected Recent Publications
  1. Phung Y, Gao W, Man YG, Nagata S, Ho M.
    MAbs. 4: 592-9, 2012. [ Journal Article ]
  2. Tang Z, Feng M, Gao W, Phung Y, Chen W, Chaudhary A, St Croix B, Qian M, Dimitrov DS, Ho M.
    Mol. Cancer Ther. 12: 416-26, 2013. [ Journal Article ]
  3. Feng M, Gao W, Wang R, Chen W, Man YG, Figg WD, Wang XW, Dimitrov DS, Ho M.
    Proc. Natl. Acad. Sci. U.S.A. 110: E1083-91, 2013. [ Journal Article ]
  4. Gao W, Kim H, Feng M, Phung Y, Xavier CP, Rubin JS, Ho M.
    Hepatology. 60: 576-87, 2014. [ Journal Article ]
  5. Gao W, Tang Z, Zhang YF, Feng M, Qian M, Dimitrov DS, Ho M.
    Nat Commun. 6: 6536, 2015. [ Journal Article ]

Biography

Dr. Mitchell Ho is Chief of the Antibody Therapy Section, Laboratory of Molecular Biology, in the NCI. Dr. Ho received his Ph.D. from the University of Illinois at Urbana-Champaign under Mariangela Segre. He won a National Research Service Award Predoctoral Fellowship from the National Institute on Drug Abuse (NIDA) for his Ph.D. thesis research on the generation of monoclonal antibodies against cocaine addiction. He was a postdoctoral fellow under Ira Pastan at the NCI and generated immunotoxins against cancer.

Dr. Ho is a recipient of the NCI Director's Intramural Innovation Award for Principal Investigators, the Mesothelioma Applied Research Foundation Grant Award, the Ovarian Cancer Research Fund Individual Investigator Award and the NIH Merit Award. He is Chair of the NIH Antibody Interest Group, and serves on the Antibody Society's Board of Distinguished Advisors. Dr. Ho regularly presents at international symposia and is a member of the organizing committees for several international conferences on therapeutic antibodies. He is Co-Chair of the Department of Biochemistry in the FAES Graduate School at the NIH. He is also a Distinguished Zijiang Visiting Chair Professor at East China Normal University.

Team

Name Position
Mingqian Feng Ph.D. Research Fellow
Wei Gao Ph.D. Postdoctoral Fellow (Visiting)
Sophia Gauthier Summer Student
Hannah Jacobs Summer Student
Nan Li Ph.D. Postdoctoral Fellow (Visiting)
Min Ni M.D. Special Volunteer
Chunguang Wang M.D. Special Volunteer
Yifan Zhang Ph.D. Postdoctoral Fellow (Visiting)