Locoregional CAR T cells for children with CNS tumors: Clinical procedure and catheter safety

Nicholas A Vitanza; Rebecca Ronsley; Michelle Choe; Casey Henson; Mandy Breedt; Adriel Barrios-Anderson; Amy Wein; Christopher Brown; Adam Beebe; Ada Kong; Danielle Kirkey; Brittany M Lee; Sarah E S Leary; Erin E Crotty; Corrine Hoeppner; Susan Holtzclaw; Ashley L Wilson; Joshua A Gustafson; Jessica B Foster; Jeffrey J Iliff; Hannah E Goldstein; Samuel R Browd; Amy Lee; Jeffrey G Ojemann; Navin Pinto; Juliane Gust; Rebecca A Gardner; Michael C Jensen; Jason S Hauptman; Julie R Park

doi:10.1016/j.neo.2022.100870

Locoregional CAR T cells for children with CNS tumors: Clinical procedure and catheter safety

Neoplasia. 2023 Feb:36:100870. doi: 10.1016/j.neo.2022.100870. Epub 2023 Jan 3.

Authors

Nicholas A Vitanza¹, Rebecca Ronsley², Michelle Choe³, Casey Henson⁴, Mandy Breedt⁴, Adriel Barrios-Anderson⁴, Amy Wein⁵, Christopher Brown⁶, Adam Beebe⁶, Ada Kong⁷, Danielle Kirkey², Brittany M Lee⁸, Sarah E S Leary², Erin E Crotty², Corrine Hoeppner⁵, Susan Holtzclaw⁵, Ashley L Wilson⁹, Joshua A Gustafson⁹, Jessica B Foster¹⁰, Jeffrey J Iliff¹¹, Hannah E Goldstein⁴, Samuel R Browd⁴, Amy Lee⁴, Jeffrey G Ojemann⁴, Navin Pinto⁸, Juliane Gust¹², Rebecca A Gardner¹³, Michael C Jensen⁹, Jason S Hauptman⁴, Julie R Park¹⁴

Affiliations

¹ Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA; Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. Electronic address: nicholas.vitanza@seattlechildrens.org.
² Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA; Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
³ Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
⁴ Division of Neurosurgery, Seattle Children's Hospital & Department of Neurological Surgery, University of Washington, Seattle, WA, USA.
⁵ Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.
⁶ Seattle Children's Therapeutics, Seattle, WA, USA; Therapeutic Cell Production Core, Seattle Children's Research Institute, Seattle, WA, USA.
⁷ Department of Pharmacy, Seattle Children's Hospital, Seattle, WA, USA.
⁸ Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA; Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.
⁹ Seattle Children's Therapeutics, Seattle, WA, USA.
¹⁰ Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
¹¹ VISN 20 Mental Illness Research, Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA; Division of Pediatric Neurology, Department of Neurology, University of Washington, Seattle, WA, USA.
¹² Division of Pediatric Neurology, Department of Neurology, University of Washington, Seattle, WA, USA; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
¹³ Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA; Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA; Seattle Children's Therapeutics, Seattle, WA, USA.
¹⁴ Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, WA, USA; Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA; Seattle Children's Therapeutics, Seattle, WA, USA.

Abstract

Central nervous system (CNS) tumors are the most common solid malignancy in the pediatric population. Based on adoptive cellular therapy's clinical success against childhood leukemia and the preclinical efficacy against pediatric CNS tumors, chimeric antigen receptor (CAR) T cells offer hope of improving outcomes for recurrent tumors and universally fatal diseases such as diffuse intrinsic pontine glioma (DIPG). However, a major obstacle for tumors of the brain and spine is ineffective T cell chemotaxis to disease sites. Locoregional CAR T cell delivery via infusion through an intracranial catheter is currently under study in multiple early phase clinical trials. Here, we describe the Seattle Children's single-institution experience including the multidisciplinary process for the preparation of successful, repetitive intracranial T cell infusion for children and the catheter-related safety of our 307 intracranial CAR T cell doses.

Keywords: B7-H3; CNS catheter; Central nervous system (CNS) tumor; Chimeric antigen receptor (CAR) T cells; EGFR; HER2; Ommaya; Ventriculoperitoneal (VP) shunt.

MeSH terms

Brain Neoplasms* / pathology
Catheters
Central Nervous System Neoplasms* / therapy
Child
Humans
Immunotherapy, Adoptive / adverse effects
Immunotherapy, Adoptive / methods
T-Lymphocytes