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

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.

PMID: 36599192
PMCID: PMC9823206
DOI: 10.1016/j.neo.2022.100870

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

Nicholas A Vitanza et al. Neoplasia. 2023 Feb.

. 2023 Feb:36:100870.

doi: 10.1016/j.neo.2022.100870. Epub 2023 Jan 3.

Authors

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.

PMID: 36599192
PMCID: PMC9823206
DOI: 10.1016/j.neo.2022.100870

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.

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Conflict of interest statement

Declaration of Competing Interest M.C.J. has interests in Umoja Biopharma, City of Hope and Juno Therapeutics, a Bristol-Myers Squibb (BMS) company. M.C.J. is a seed investor and holds ownership equity in Umoja, serves as a member of the Umoja Joint Steering Committee, and is a Board Observer of the Umoja Board of Directors. M.C.J. is an inventor of patents licensed to Umoja Biopharma, City of Hope, and Juno Therapeutics. The remaining authors declare no competing financial interests. R.A.G. serves on a study steering committee for and is an inventor on a patent licensed to Juno Therapeutics, a Bristol Myers Squibb company, has served on advisory boards for Novartis and Sobi, and is a consultant for Crispr Therapeutics. A.J.J. and J.B.F. are inventors on issued and pending patents related to CAR T cell therapies. All other authors declare no competing interests.

Figures

Fig 1 — **Fig. 1**
Intracranial dosing procedure. ∼45 min after a topical anesthetic agent is applied, (A) the Ommaya or shunt reservoir site is sterilized with betadine, (B) a 25-guage butterfly needle is inserted, and 0.5 mL preservative-free normal saline (PFNS) is infused. The sterile syringe of PFNS is removed and (C) a new 10 mL syringe is connected to withdraw CSF for clinical and correlative studies. That syringe is removed, and (D) a syringe with CAR T cells is connected. Finally, that syringe is removed and a syringe with 2.5 mL PFNS is connected and infused, after which the needle, with the syringe connected, is removed.

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous