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Clonal kinetics and single cell transcriptional profiling of adoptively transferred CD19-specific CD8+ CAR-T cells in adults with B cell malignancies

ABSTRACT: Clonal kinetics and single cell transcriptional profiling of adoptively transferred CD19-specific CD8+ CAR-T cells in adults with B cell malignancies

PROVIDER: PRJNA517816 | ENA |

REPOSITORIES: ENA

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Clonal kinetics and single cell transcriptional profiling of adoptively transferred CD19-specific CD8+ CAR-T cells in adults with B cell malignancies

Project description:Lymphodepletion chemotherapy followed by infusion of T cells modified to express a CD19-targeting chimeric antigen receptor (CAR) has produced remarkable anti-tumor responses in patients with B cell malignancies. However, little is known about the clonal composition and transcriptional heterogeneity of CAR-T cells in the infusion products (IP) and clonal kinetics after adoptive transfer. We performed single-cell RNA sequencing (scRNA-seq) on CD8+ CAR-T cells isolated from the IP and the blood of patients treated on a phase 1 clinical trial (NCT01865617) with lymphodepletion chemotherapy and a defined formulation of CD4+ and CD8+ CD19-specific CAR-T cells. Infused CD8+ CAR-T cells displayed transcriptional heterogeneity which declined after adoptive transfer, coincident with early expression of genes associated with activation. We identified four transcriptionally distinct CAR-T cell subsets in the IP and found that these subsets differed in their contributions to the CAR-T cell population detected in blood after infusion. Better understanding of the kinetics of clonal expansion of CAR-T cells after adoptive transfer may provide insight into strategies to improve CAR-T cell immunotherapy.

2019-11-22 | GSE125881 | GEO

B cell CD19 is widely transferred between immune cells [M]

Project description:When immune cells interact, they frequently exchange membrane-bound antigens. Our evolving understanding of these processes challenges the cellular specificity of lineage markers and therapeutically applied monoclonal antibodies. We here report that CD19, an assumingly exclusive B cell marker, is transferred via trogocytosis when B cells activate T cells as antigen-presenting cells. In a B cell-driven model of experimental autoimmune encephalomyelitis, CD19+ T cells accordingly expanded and showed enhanced features of activation, differentiation, and encephalitogenicity. A similar profile of augmented pathogenic properties of CD19+ T cells was detected in patients with chronic CNS demyelination. Here, CD19+ T cells were found to be concomitantly depleted by inebilizumab, an approved anti-CD19 antibody, which may support its effectiveness. Furthermore, we report that CD19 is found on myeloid cells after phagocytosis of apoptotic B cells. These results highlight the commonness of membrane and antigen transfer between interacting cells and provide instrumental considerations for monoclonal antibody therapies.

2026-06-03 | GSE286404 | GEO

B cell CD19 is widely transferred between immune cells [CD11b+]

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Combination therapy with oncolytic virus and adoptively transferred T cells or mRNA vaccine amplifies antitumor effects [scRNA-Seq]

Project description:Adoptive T-cell therapy or oncolytic virotherapy has made significant progress, but the efficacy was limited by the lack of infiltration into solid tumors when used alone. Here, an oncolytic virus (rVSV-LCMVG) was designed and combined with adoptively transferred T cells. By turning cold tumors hot, in B16 tumor-bearing mice, combination therapy showed superior antitumor effects than monotherapy, whether rVSV-LCMVG was administered intratumorally or intravenously. Combination therapy significantly increased cytokine and chemokine levels within tumors and sensitized refractory tumors by boosting T-cell recruitment, down-regulating the expression of PD1, and restoring effector-T cell function. To offer a combination therapy with greater translational value, mRNA vaccines were introduced to induce tumor-specific T cells instead of adoptively transferred T cells, and exhibited comparable amplified anti-tumor effects. This study proposed a rational combination therapy of oncolytic virus with adoptive T-cell transfer or mRNA vaccines encoding tumor-associated antigens, in terms of synergistic efficacy and mechanism.

2024-03-15 | GSE235290 | GEO

Combination therapy with oncolytic virus and adoptively transferred T cells or mRNA vaccine amplifies antitumor effects [RNA-Seq]

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B cell CD19 is widely transferred between immune cells [CD11b+]

Project description:B cell CD19 is widely transferred between immune cells [CD11b+]

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B cell CD19 is widely transferred between immune cells [M]

Project description:B cell CD19 is widely transferred between immune cells [M]

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TLR9-activated B cells imprint adoptively transferred CD8+ T cells with potent tumor immunity and persistence

Project description:Here we report a new way to reverse the tolerant state of adoptively transferred CD8+ T cells against melanoma through ex vivo expansion with the TLR9 agonist CpG. CpG-generated T cells elicited potent immunity without co-administration of high dose IL-2 or vaccination, which are adjuvants classically required to effectively treat solid tumors. CpG-expanded T cells exhibited an IL-2RhighICOShighCD39low phenotype ex vivo and engrafted robustly in vivo. In culture, B cells were the only cell type essential for imprinting T cells with this phenotype and potent tumor immunity. CpG agonists targeting B cells, but not dendritic cells, generated CD8+ T cell products with remarkable antitumor properties. Purified B cells were sufficient to mediate the CpG-associated changes in T cells. These findings reveal a vital role for B cells in the generation of effective antitumor T cells and have immediate implications for profoundly improving immunotherapy for patients.

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Tumor-infiltrating, adoptively transferred BATF-overexpressing CD8 T cells analyzed via bulk RNA-seq

Project description:Tumor-infiltrating, adoptively transferred BATF-overexpressing CD8 T cells analyzed via bulk RNA-seq

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Gene expression in adoptively transferred OT-II cells isolated from mesenteric lymph nodes of control or MHCIIB-/- chimeras 5 days post-immunization with OVA and polyI:C.

Project description:To gain insight into the transcriptional program conferred to Th cells by B cells, we conducted microarray gene expression analyses of adoptively transferred OT-II cells sorted from the mesenteric lymph nodes of bone marrow chimeric control and MHCIIB-/- mice 5 days after immunization with OVA and polyI:C.

2021-11-11 | E-MTAB-11165 | biostudies-arrayexpress

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