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A novel predictive algorithm to personalize autologous T-cell harvest for chimeric antigen receptor T-cell manufacture.
O'Reilly, Maeve A; Malhi, Aman; Cheok, Kathleen P L; Ings, Stuart; Balsa, Carmen; Keane, Helen; Jalowiec, Katarzyna; Neill, Lorna; Peggs, Karl S; Roddie, Claire.
Afiliação
  • O'Reilly MA; University College London Cancer Institute, London, UK; Department of Hematology, University College London Hospital, London, UK. Electronic address: maeve.o'reilly@ucl.ac.uk.
  • Malhi A; Cancer Research UK & University College London Cancer Trials Center, University College London, London, UK.
  • Cheok KPL; Department of Hematology, University College London Hospital, London, UK.
  • Ings S; Department of Hematology, University College London Hospital, London, UK.
  • Balsa C; Department of Hematology, University College London Hospital, London, UK.
  • Keane H; Department of Hematology, University College London Hospital, London, UK.
  • Jalowiec K; Department of Hematology, University College London Hospital, London, UK.
  • Neill L; Department of Hematology, University College London Hospital, London, UK.
  • Peggs KS; University College London Cancer Institute, London, UK; Department of Hematology, University College London Hospital, London, UK.
  • Roddie C; University College London Cancer Institute, London, UK; Department of Hematology, University College London Hospital, London, UK.
Cytotherapy ; 25(3): 323-329, 2023 03.
Article em En | MEDLINE | ID: mdl-36513573
BACKGROUND AIMS: The most widely accepted starting materials for chimeric antigen receptor T-cell manufacture are autologous CD3+ T cells obtained via the process of leukapheresis, also known as T-cell harvest. As this treatment modality gains momentum and apheresis units struggle to meet demand for harvest slots, strategies to streamline this critical step are warranted. METHODS: This retrospective review of 262 T-cell harvests, with a control cohort of healthy donors, analyzed the parameters impacting CD3+ T-cell yield in adults with B-cell malignancies. The overall aim was to design a novel predictive algorithm to guide the required processed blood volume (PBV) (L) on the apheresis machine to achieve a specific CD3+ target yield. RESULTS: Factors associated with CD3+ T-cell yield on multivariate analysis included peripheral blood CD3+ count (natural log, ×109/L), hematocrit (HCT) and PBV with coefficients of 0.86 (95% confidence interval [CI], 0.80-0.92, P < 0.001), 1.30 (95% CI, 0.51-2.08, P = 0.001) and 0.09 (95% CI, 0.07-0.11, P < 0.001), respectively. The authors' model, incorporating CD3+ cell count, HCT and PBV (L), with an adjusted R2 of 0.87 and root-mean-square error of 0.26 in the training dataset, was highly predictive of CD3+ cell yield in the testing dataset. An online application to estimate PBV using this algorithm can be accessed at https://cd3yield.shinyapps.io/cd3yield/. CONCLUSIONS: The authors propose a transferrable model that incorporates clinical and laboratory variables accessible pre-harvest for use across the field of T-cell therapy. Pending further validation, such a model may be used to generate an individual leukapheresis plan and streamline the process of cell harvest, a well-recognized bottleneck in the industry.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de Antígenos Quiméricos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Adult / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de Antígenos Quiméricos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Adult / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article