CD19 expression

present data from pretreatment tumor biopsies taken on the ZUMA-7 trial. Their results identify tumor microenvironment (TME) contexts and level of CD19 expression as prognostic indicators for responses to axicabtagene ciloleucel (axi-cel).

The findings prompt reflection also on the broader role of epigenetics in decoupling of replication from lineage differentiation activation by the B cell lineage master transcription factor hub. Such oncogenesis and resistance mechanisms, being predictable and epigenetic, offer practical opportunities for intervention, potentially non-cross-resistant and safe vis-à-vis present cytotoxic and CAR-T treatments.

P1/2, N=66, Not yet recruiting, National Cancer Institute (NCI)

P1, N=55, Terminated, Fred Hutchinson Cancer Center | Active, not recruiting --> Terminated; Terminated due to slow enrollment and end of funding

Compared to unmodified T cells, CD19 CAR T cells effectively eradicated Nalm6 cells. Taken together, we can show that lymphocytes isolated from LRSCs of plateletpheresis sets can be efficiently used for the generation of functional CAR T cells for experimental purposes.

P=N/A, N=85, Not yet recruiting, University Hospital, Montpellier

P2, N=27, Completed, Institute of Hematology and Blood Transfusion, Czech Republic | Active, not recruiting --> Completed | N=45 --> 27 | Trial completion date: Jul 2024 --> Feb 2024

P1, N=85, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Apr 2024

Moreover, the knockdown of ACAT1 led to better anti-tumor efficacy of anti-CD19 CAR-T cells in the B-cell lymphoma mice model. Our study demonstrates novel CAR-T cells containing ACAT1 shRNA with improved efficacy compared to conventional anti-CD19-CAR-T cells in vitro and in vivo.

Despite the success of CAR-T therapy for NHL, challenges include adverse side effects as well as extrinsic and intrinsic mechanisms of tumor resistance that lead to suboptimal outcomes. Overall, CAR-T cell therapies have improved clinical outcomes in NHL patients and generated optimism around their future applications.

P2, N=53, Active, not recruiting, Northwestern University | Trial completion date: May 2023 --> May 2027

Compared to GBM spheroids, the presence of pericytes significantly enhanced CD19 CAR-iNK cell migration towards GBM and reduced proliferation. These results underline the efficacy of CD19 CAR-iNK cells in targeting pericytes within the GBM TME, suggesting their potential therapeutic value for GBM treatment.

This study supports enhancement of therapeutic potency of CAR-Vδ2 T cells through a manufacturing improvement.

P1, N=85, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Mar 2025 --> Mar 2024

P=N/A, N=144, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Recruiting --> Active, not recruiting | N=240 --> 144 | Trial primary completion date: Jun 2028 --> Feb 2024

The creation of CD19/CD20 dual-targeted CAR-NK cells addressed the risk of tumor escape due to antigen heterogeneity in ALL, offering efficient and safe 'off-the-shelf' cell products. These cells demonstrate efficacy in targeting CD20 and/or CD19 antigens in ALL, laying an experimental foundation for their application in ALL treatment.

P1, N=6, Active, not recruiting, Children's Hospital of Fudan University | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Oct 2023 --> Oct 2024

P1, N=85, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Mar 2024 --> Mar 2025

MRD combined with CD19 might optimize PRT choices for adult t(8;21) AML patients in CR1.

P1/2, N=50, Not yet recruiting, Juventas Cell Therapy Ltd. | Initiation date: Oct 2023 --> Aug 2024

Moreover, in an in vivo bilateral murine tumor model, they exhibited the capability to effectively restrain tumor growth. Overall, CD19-SynNotch PDbody-CAR T cells represent a distinct development over previously published designs due to their increased efficacy, proliferative capability, and mitigation of off-tumor toxicity for solid tumor treatment.

Finally, we developed a current good manufacturing practices-compliant clinical-scale protocol for producing Hu19-CAR T from PBMC of CLL patients. These Hu19-CAR T exhibited a full range of in vitro functions and eliminated leukemia from mice.

P1, N=36, Recruiting, Sumithira Vasu | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=50, Recruiting, PETHEMA Foundation | Not yet recruiting --> Recruiting | Initiation date: Mar 2024 --> Nov 2023

P3; Initiation date: Jan 2024 --> Apr 2024

Our findings support that the efficacy of Fc-engineered CD19 antibodies may be substantially enhanced by a combination with CD47 blockade. This suggests that the combination may be a promising therapy option for BCP-ALL, especially in relapsed patients and/or patients refractory to CD19-directed therapy.

P1, N=56, Active, not recruiting, Crystal Mackall, MD | Recruiting --> Active, not recruiting

P2, N=50, Not yet recruiting, PETHEMA Foundation

We observed no weight loss, severe hematological toxicity or NK cell-mediated death in the BNDG mice. The MUC1-targeted CAR-NK cells had significant efficacy against human OTSCC, and their promising therapeutic response warrants further clinical trials.

We found Lonca is an effective treatment for R/R DLBCL regardless of CD19 expression by immunohistochemistry. These results provide the basis for future studies addressing CD19-targeted agent sequencing.

The results of the study have shown that cytotoxic drugs can alter the expression of antigens that are important for immunotherapy. Importantly, daunorubicin, prednisolone and vincristine caused down-modulation of CD19 and CD58, suggesting that these drugs are better avoided during bridging therapy prior to bispecific antibodies or CAR-T cell therapy. In addition, immunophenotypic changes on blast cells induced by different drugs could also influence risk-based treatment assignment.

One week after intraperitoneal implantation of CT26-CD19-FLUC-GFP cells into mice, FLUC expression in the peritoneal region could be detected. These results indicate the successful establishment of a stable CT26 cell line expressing CD19-FLUC-GFP, which can be specifically targeted by CD19 CAR-T cells.

CD19low resistant cells exhibited preserved B cell receptor signaling and were more sensitive to both BTK and MEK inhibition. These data demonstrate that resistance to CD19 immunotherapies can result in decreased expression of both CD19 and CD22 and can result in dependency on BTK pathways.

P1, N=36, Recruiting, Synthekine | Trial primary completion date: Jun 2024 --> Jun 2026

With the simultaneous detection of the CAR-T cells and the B cell malignancy in patient peripheral blood, the HDSCA-HemeCAR workflow may be considered for risk monitoring and patient management.

Dual targeting can the accomplished through co-administration of two separate products, co-transduction with two different vectors, bicistronic cassettes or tandem receptors. In this manuscript, we review the pros and cons of each strategy and the clinical results obtained so far.

P1, N=24, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jan 2024 --> Dec 2024

P2, N=168, Recruiting, Miltenyi Biomedicine GmbH | Trial completion date: Dec 2024 --> Jul 2027 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=20, Recruiting, Stanford University | Phase classification: P1b --> P1

Our results demonstrate expansion and homing of CAR-T cells into the CNS in SNCSL patients. Local production of chemokines such as IP-10 may support CNS infiltration by CAR-T cells but also carry the potential of amplifying local toxicity. Future studies investigating numbers, phenotype, and function of CAR-T in the different body compartments of SNSCL patients receiving CAR-T will help to improve local delivery of "fit" and highly tumor-reactive CAR-T with low off-target reactivity into the CNS.

We also show that 4DRCA can distinguish BCR-ABL1 fusion transcript positive B-cell acute lymphoblastic leukemia cells with or without CD19 protein expression. The accessibility and extensibility of 4DRCA render it broadly applicable to other cell-based diagnostic workflows, enabling sensitive and accurate single-cell RNA and protein profiling.

However, salvage therapies for relapsed large B-cell lymphoma after CART19 cell therapy have not been fully explored and are conducted based on clinicians' case-by-case decisions. In this review, we will focus on salvage therapies reported to date and discuss the management of relapsed/refractory large B-cell lymphomas after CART19 cell therapy.