Abstract B051: Marrow and peripheral blood cytokine architecture differences between pediatric patients receiving CD19- and CD22-directed CART
Notice bibliographique
Résumé
Abstract Introduction: Chimeric antigen receptor T-cell (CART) targeting CD19 (CART19) have revolutionized therapy for relapsed/refractory pediatric B-cell acute lymphoblastic leukemia (B-ALL). However, not all children are cured with CD19-directed CART, leading to the use of CD22-directed CART (CART22) as an alternative therapy. To better understand differences in outcome and toxicity following CART19 and CART22 we used high-throughput protein and transcriptional techniques to understand differences in cytokine architecture. Methods: We used a proximity extension assay (Olink Signature 100 T48, Olink, Uppsala, Sweden) to measure 48 proteins from paired peripheral blood (PB) and bone marrow (BM) serum from 20 patients (N=10 CART19, N=10 CART22). We performed single cell RNA sequencing (scRNAseq) on pre-infusion peripheral blood mononuclear cells (PBMCs; N=3 CART19, N=4 CART22) and pre-infusion bone marrow mononuclear cells (BMMCs; N=3 CART19, N=4 CART22). Croypreserved cells were thawed. Approximately ten thousand cells from each sample were pooled into a single volume and then taken into a single cell RNA-Seq assay using the Chromium NextGem Single Cell 3' GEM, Library & Gel Bead Kit v3.1(10X Genomics). Sequencing libraries were run on Bioanalyzer 2100 and quantified with KAPA library quantification kit (Roche 07960140001) prior to sequencing on Illumina NovaSeq6000 with 28:10:10:90 paired-end configuration. Results: Samples were obtained from patients treated on clinical trials of CART19 (NCT01626495, NCT02906371) and CART22 (NCT02650414). There was no difference in pre-infusion disease burden between CART19 and CART22 patients. All patients who received CART22 had previously been treated with CART19 or the CD19 directed bispecific T-cell engaging antibody blinatumomab. Pre-treatment marrow serum from patients who went on to receive CART22 had higher levels of the proteins CSF3, IL10, CXCL9, IL6, CXCL8 and CXCL10, implying that previous treatment with CART19 impacted the marrow environment. Pre-treatment marrow cellular populations also differed between CART19 and CART22 patients. Patients who went on to receive CART22 had a higher proportion of CD16+ monocytes then CART19 patients. Three distinct clusters of CD16+ monocytes were identified with unique transcriptional profiles. We previously demonstrated that the anti-inflammatory cytokine IL-10 was higher in the peripheral blood of patients who went on to receive CART22. Measured IL-10 protein levels were higher in both BM and PB serum. Pre-treatment PBMC expression of IL-10 measured by scRNAseq did not differ appreciably between patients who went on to receive CART19 and those who went on to receive CART22. However, IL-10 expression in BMMCs was higher in patients who went on to receive CART22, implying that measured IL-10 differences have a marrow cellular source. Conclusions: Using high throughput protein measurement techniques and scRNAseq we demonstrate clear differences in the pre-infusion cytokine and cellular architecture of patients treated with CART19 or CART22. Citation Format: Caroline Diorio, Lahari Uppuluri, Anusha Thadi, Regina Myers, Rawan Shraim, Amanda Dinofia, Zachary Martinez, Amira Elhachimi, Joseph Fraietta, Vanessa Gonzalez, Vivian Yi, Haley Newman, Andrew Hughes, Kai Tan, Stephan Grupp, David T. Teachey. Marrow and peripheral blood cytokine architecture differences between pediatric patients receiving CD19- and CD22-directed CART [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B051.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».