GD2-specific CAR T cells encapsulated in an injectable hydrogel control retinoblastoma and preserve vision

Kai Wang; Yuhui Chen; Sarah Ahn; Min Zheng; Elisa Landoni; Gianpietro Dotti; Barbara Savoldo; Zongchao Han

doi:10.1038/s43018-020-00119-y

GD2-specific CAR T cells encapsulated in an injectable hydrogel control retinoblastoma and preserve vision

Nat Cancer. 2020 Oct;1(10):990-997. doi: 10.1038/s43018-020-00119-y. Epub 2020 Oct 12.

Authors

Kai Wang^#¹, Yuhui Chen^#², Sarah Ahn^#^{2

3}, Min Zheng¹, Elisa Landoni², Gianpietro Dotti^{2

3}, Barbara Savoldo^{4

5}, Zongchao Han^{6

7

8}

Affiliations

¹ Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
² Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
³ Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴ Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. bsavoldo@med.unc.edu.
⁵ Department of Pediatric Hematology-Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. bsavoldo@med.unc.edu.
⁶ Department of Ophthalmology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. zongchao@med.unc.edu.
⁷ Carolina Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. zongchao@med.unc.edu.
⁸ Division of Pharmacoengineering & Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. zongchao@med.unc.edu.

^# Contributed equally.

Abstract

Retinoblastoma (RB) is a pediatric retinal tumor that overexpresses the ganglioside GD2. Although it is treatable in patients with early diagnosis, patients may lose one or two eyes. We generated GD2-specific chimeric antigen receptor T lymphocytes (GD2.CAR-Ts) and locally delivered them to mice with an in-situ grafting RB. When used in combination with the local release of interleukin (IL)-15 and an injectable hydrogel, we showed that GD2.CAR-Ts successfully eliminate RB tumor cells without impairment of the mouse vision.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Gangliosides
Humans
Hydrogels
Mice
Retinal Neoplasms* / therapy
Retinoblastoma* / therapy
T-Lymphocytes

Substances

Gangliosides
Hydrogels

Abstract

Publication types

MeSH terms

Substances

Grants and funding