دورية أكاديمية

Unlocking Predictive Power: Quantitative Assessment of CAR-T Expansion with Digital Droplet Polymerase Chain Reaction (ddPCR)

التفاصيل البيبلوغرافية
العنوان: Unlocking Predictive Power: Quantitative Assessment of CAR-T Expansion with Digital Droplet Polymerase Chain Reaction (ddPCR)
المؤلفون: Galli E., Viscovo M., Pansini I., Hohaus S., Bellesi S., Chiusolo P.
المساهمون: Galli, Eugenio, Viscovo, Marcello, Fosso, F., Pansini, Ilaria, Di Cesare, G., Iacovelli, C., Maiolo, E., Sora, F., Hohaus, Stefan, Sica, S., Bellesi, Silvia, Chiusolo, Patrizia
بيانات النشر: Multidisciplinary Digital Publishing Institute (MDPI)
سنة النشر: 2024
المجموعة: Università Cattolica del Sacro Cuore: PubliCatt
مصطلحات موضوعية: B-cell lymphoma, CAR-T cells, digital droplet PCR, Settore MED/15 - MALATTIE DEL SANGUE
الوصف: Flow cytometry (FCM) and quantitative PCR (qPCR) are conventional methods for assessing CAR-T expansion, while digital droplet PCR (ddPCR) is emerging as a promising alternative. We monitored CAR-T transcript expansion in 40 B-NHL patients post-infusion of CAR-T products (axi-cel; tisa-cel; and brexu-cel) with both His-Tag FCM and ddPCR techniques. Sensitivity and predictive capacity for efficacy and safety outcomes of ddPCR were analyzed and compared with FCM. A significant correlation between CAR-T counts determined by FCM and CAR transcripts assessed by ddPCR (p < 0.001) was observed. FCM revealed median CD3+CAR+ cell counts at 7, 14, and 30 days post-infusion with no significant differences. In contrast, ddPCR-measured median copies of CAR-T transcripts demonstrated significant lower copy numbers in tisa-cel recipients compared to the other products at day 7 and day 14. Patients with a peak of CAR transcripts at day 7 exceeding 5000 copies/microg gDNA, termed “good CAR-T expanders”, were more likely to achieve a favorable response at 3 months (HR 10.79, 95% CI 1.16–100.42, p = 0.036). Good CAR-T expanders showed superior progression-free survival at 3, 6, and 12 months compared to poor CAR-T expanders (p = 0.088). Those reaching a peak higher than 5000 copies/microg gDNA were more likely to experience severe CRS and ICANS. DdPCR proves to be a practical method for monitoring CAR-T expansion, providing quantitative information that better predicts both treatment outcomes and toxicity.
نوع الوثيقة: article in journal/newspaper
اللغة: English
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/38473919; info:eu-repo/semantics/altIdentifier/wos/WOS:001183352800001; volume:25; issue:5; firstpage:N/A; lastpage:N/A; issueyear:2024; journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; https://hdl.handle.net/10807/274574Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85187782506
DOI: 10.3390/ijms25052673
الإتاحة: https://doi.org/10.3390/ijms25052673Test
https://hdl.handle.net/10807/274574Test
رقم الانضمام: edsbas.483FB018
قاعدة البيانات: BASE