CD19 expression

Mixed phenotype acute leukemia (MPAL) is a rare type of malignant hematologic disease. Its diagnosis is based on the comprehensive evaluation of bone marrow cell morphology, immunophenotype, molecular and cytogenetic features.

P1, N=20, Active, not recruiting, Institute of Hematology & Blood Diseases Hospital, China | Recruiting --> Active, not recruiting | N=34 --> 20

In conclusion, we demonstrated the specific targeting and visualization of CD19+ B-NHL in mice and humans by CD19-immunoPET. The intra- and interindividual heterogeneous 64Cu-αCD19 uptake patterns of lymphoma lesions indicate variability in CD19 expression, suggesting the potential of CD19-immunoPET as a novel tool to guide CD19-directed therapies.

Loncastuximab tesirine was more potent than other anti-CD19 ADCs (coltuximab ravtansine, huB4-DGN462), albeit the pattern of activity across cell lines was correlated. Loncastuximab tesirine activity was also largely correlated with cell line sensitivity to R-CHOP...Our data support the further development of loncastuximab tesirine as a single agent and in combination for patients affected by mature B-cell neoplasms. The results also highlight the importance of CD19 expression and the existence of lymphoma populations characterized by resistance to multiple therapies.

P1, N=11, Active, not recruiting, University of Colorado, Denver | Trial completion date: Dec 2023 --> Dec 2024

The use of bidirectional promoters in a single vector offers advantages of size and robust CAR expression with the potential to expand use in other forms of gene therapies like CAR T cells.

This study reports a rare case of TdT positive "double hit" HGBL following the treatment of concurrent FL/DLBCL and highlights the mutation characteristics. Collectively, this study will help enrich the knowledge of TdT positive "double hit" HGBL transformed from FL/DLBCL.

Additionally, we obtained the purified CD8+ T cells by optimizing a shorter version of the CD8-binding aptamer to generate anti-FITC CD8-CAR-T cells, which combined with the CD4-FITC-ST switch module (anti-CD4) to eliminate the CD4-positive tumor cells in vitro and in vivo. Overall, we established a novel safety switch module by site-specific conjugation to enhance the antitumor function of universal CAR-T cells, thereby expanding the application scope of CAR-T therapy and improving its safety and efficacy.

The anti-CD19 monoclonal antibody tafasitamab, paired with the immunomodulator lenalidomide, mediates antibody-dependent cellular toxicity and cellular phagocytosis; the antibody-drug conjugate loncastuximab tesirine delivers the DNA-cross-linking agent tesirine via CD19 binding and internalization; and CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) products are engineered from autologous T cells. To date, clinical evidence on the effect of anti-CD19 therapy prior to CAR-T is restricted to small case series. Prospective studies and detailed analyses to understand how pre- and post-treatment CD19 expression correlates with clinical responses to subsequent CD19-directed therapy are needed to fully maximize treatment strategies.

P3, N=680, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Apr 2024 --> Jul 2024

P1/2, N=20, Completed, Celgene | Recruiting --> Completed | N=121 --> 20 | Trial completion date: Dec 2024 --> Jan 2024 | Trial primary completion date: Dec 2024 --> Jan 2024

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).

Historically, B and T cell (B-T cell) co-interaction was targeted through different pathways such as alemtuzumab, abatacept, and dapirolizumab with variable impact on B cell depletion (BCD), whereas the majority of patients with AID including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and organ transplantation benefit from targeted BCD with anti-CD20 monoclonal antibodies such as rituximab, ocrelizumab or ofatumumab...In the treatment of cancer, chimeric antigen receptor (CAR) T cell therapy and T cell engagers (TCE) that recruit T cells to induce B cell cytotoxicity have delivered promising results for anti-CD19 CAR T cell therapies, the CD19 TCE blinatumomab and CD20 TCE such as mosunetuzumab, glofitamab or epcoritamab. Limited evidence suggests that anti-CD19 CAR T cell therapy may be effective in managing refractory AID whereas we await evaluation of TCE for use in non-oncological indications. Therefore, here, we discuss the potential mechanistic advantages of novel therapies that rely on T cells as effector cells to disrupt B-T cell collaboration toward overcoming rituximab-resistant AID.

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.