Nina Nooteboom

Ms. Nina Nooteboom

orcid

Research Focus & Metrics

Academic Career Length

1Year (2026-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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28 March 2026 in Pharmaceutics
Verified
Journal Article
Open access
PDF file
AÖAysenur Öner
Aysenur Öner
NNNina Nooteboom
Nina Nooteboom
LOLinette Oosting
Linette Oosting
JKJos Kosterink
Jos Kosterink
BDBart Dekkers
Bart Dekkers
Bahez GarebBahez Gareb
Bahez Gareb
Background/Objectives: Point-of-care (PoC) manufactured fresh chimeric antigen receptor (CAR)-T cells are typically formulated in hypothermic preservation formulations (HPFs) and stored under hypothermic conditions (2–8 °C) until administered to the patient. However, in current HPFs the shelf life of fresh CAR-T cells is short (~24–36 h) due to limited CAR-T cell stability, which poses significant time constraints on manufacturing procedures and logistics. The objective of this study was to improve the stability and extend the shelf life of fresh clinical-grade CAR-T cell drug products (DPs). Methods: A novel HPF was developed by supplementing a base HPF with the novel excipient SUL-138, which stabilizes mitochondria during hypothermic storage and subsequent rewarming, alone or in combination with endogenous mitochondrial substrates. This panel of HPFs was first screened for their stability-improving characteristics in the model cell line Jurkat cells. Subsequently, HPFs were assessed for their stability-improving characteristics of clinical-grade CD19 CAR-T cell DPs. Critical quality attributes, including CAR-T cell viability, T-cell differentiation state, exhaustion markers, and functional potency were evaluated in a good manufacturing practice (GMP)-compliant stability study up to 72 h. Results: For Jurkat cells, HPFs supplemented with SUL-138 and a combination of glucose, glutamine, and succinate demonstrated the greatest stability improvement at 2–8 °C, improving cell viability from ~1% to >85% after 72 h. For CAR-T cells, supplementation of HPFs with SUL-138 alone demonstrated the greatest improvement, resulting in a CAR-T cell viability from ~40% to >85% after 72 h of storage at 2–8 °C, while no additional benefits from mitochondrial substrates were observed. The novel HPF did not significantly impact CAR-T cell potency test results, T cell subset distribution, or exhaustion markers compared to control. Conclusions: A novel clinical-grade HPF that significantly improved fresh CAR-T cell stability during hypothermic storage was developed. This novel HPF can aid in the establishment of GMP-compliant and PoC CAR-T cell manufacturing platforms.