[en] T cell immunotherapies have revolutionized treatment for a subset of cancers. Yet, a major hurdle has been the lack of facile and predicative preclinical animal models that permit dynamic visualization of T cell immune responses at single-cell resolution in vivo. Here, optically clear immunocompromised zebrafish were engrafted with fluorescent-labeled human cancers along with chimeric antigen receptor T (CAR T) cells, bispecific T cell engagers (BiTEs), and antibody peptide epitope conjugates (APECs), allowing real-time single-cell visualization of T cell-based immunotherapies in vivo. This work uncovered important differences in the kinetics of T cell infiltration, tumor cell engagement, and killing between these immunotherapies and established early endpoint analysis to predict therapy responses. We also established EGFR-targeted immunotherapies as a powerful approach to kill rhabdomyosarcoma muscle cancers, providing strong preclinical rationale for assessing a wider array of T cell immunotherapies in this disease.
Disciplines :
Oncology
Author, co-author :
Yan, Chuan ; Molecular Pathology Unit, Massachusetts General Research Institute, Charlestown, MA ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA ; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA ; Harvard Stem Cell Institute, Cambridge, MA
Yang, Qiqi ; Molecular Pathology Unit, Massachusetts General Research Institute, Charlestown, MA ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA ; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA ; Harvard Stem Cell Institute, Cambridge, MA
Zhang, Songfa ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA
Millar, David G ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA
Alpert, Eric J ; Molecular Pathology Unit, Massachusetts General Research Institute, Charlestown, MA ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA ; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA ; Harvard Stem Cell Institute, Cambridge, MA
Do, Daniel ; Molecular Pathology Unit, Massachusetts General Research Institute, Charlestown, MA ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA ; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA ; Harvard Stem Cell Institute, Cambridge, MA
Bacquelaine Veloso, Alexandra ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie - Immunologie ; Molecular Pathology Unit, Massachusetts General Research Institute, Charlestown, MA ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA ; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA ; Harvard Stem Cell Institute, Cambridge, MA
Brunson, Dalton C ; Molecular Pathology Unit, Massachusetts General Research Institute, Charlestown, MA ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA ; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA ; Harvard Stem Cell Institute, Cambridge, MA
Drapkin, Benjamin J ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA
Stanzione, Marcello ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA
Scarfò, Irene ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA
Moore, John C ; Molecular Pathology Unit, Massachusetts General Research Institute, Charlestown, MA ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA ; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA ; Harvard Stem Cell Institute, Cambridge, MA
Iyer, Sowmya ; Molecular Pathology Unit, Massachusetts General Research Institute, Charlestown, MA ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA ; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA ; Harvard Stem Cell Institute, Cambridge, MA
Qin, Qian ; Molecular Pathology Unit, Massachusetts General Research Institute, Charlestown, MA ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA ; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA ; Harvard Stem Cell Institute, Cambridge, MA
Wei, Yun ; Molecular Pathology Unit, Massachusetts General Research Institute, Charlestown, MA ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA ; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA ; Harvard Stem Cell Institute, Cambridge, MA
McCarthy, Karin M ; Molecular Pathology Unit, Massachusetts General Research Institute, Charlestown, MA ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA ; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA ; Harvard Stem Cell Institute, Cambridge, MA
Rawls, John F ; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC
Dyson, Nick J ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA
Cobbold, Mark ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA ; Early Oncology R&D, AstraZeneca, Gaithersburg, MD
Maus, Marcela V ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA
Langenau, David M ; Molecular Pathology Unit, Massachusetts General Research Institute, Charlestown, MA ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA ; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA ; Harvard Stem Cell Institute, Cambridge, MA
This work is supported by National Institutes of Health grants R24OD016761 (D.M. Langenau), R01CA154923 (D.M. Langenau), R01CA215118 (D.M. Langenau), and R01CA211734 (D.M. Langenau); the Liddy Shriver Sarcoma Initiative (D.M. Langenau); the Massachusetts General Hospital Research Scholars Program (D.M. Langenau), U01CA220323 (N.J. Dyson); the Tosteson & Fund for Medical Discovery Fellowship from Massachusetts General Hospital (C. Yan); and the Alex’s Lemonade Stand Foundation Young Investigator Award (C. Yan). This work is supported by National Institutes of Health
grants R24OD016761 (D.M. Langenau), R01CA154923 (D.M.
Langenau), R01CA215118 (D.M. Langenau), and R01CA211734
(D.M. Langenau); the Liddy Shriver Sarcoma Initiative
(D.M. Langenau); the Massachusetts General Hospital Research
Scholars Program (D.M. Langenau), U01CA220323
(N.J. Dyson); the Tosteson & Fund for Medical Discovery
Fellowship from Massachusetts General Hospital (C. Yan);
and the Alex’s Lemonade Stand Foundation Young Investigator
Award (C. Yan).
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