CD19 expression

Based on specificity, efficacy, and loss of the target antigen, CARLY3 represents a potential novel CAR treatment for NHL.

The immunophenotype and the landscape of cooperative gene alterations in AML with RUNX1::CBFA2T2 resemble those of AML with RUNX1::RUNX1T1, including expression of CD19, cooperative gene alterations in signaling pathway (JAK2), epigenetic/chromatin and cell cycle regulation (TET2, SMC3, and CDKN2A/B), and additional chromosomal abnormalities (trisomies 8 and 15). This case study provides insights into the pathogenesis of this rare subtype of AML.

These findings underscore the critical role of CD19 within the tumor microenvironment, suggesting its potential as a biomarker and a therapeutic target in specific types of cancer.

P1, N=10, Recruiting, Institute of Hematology and Blood Transfusion, Czech Republic | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

Multi-target approaches, e.g. the bispecific BCMA×CD19 CAR-T product GC012F, are advancing through clinical development with encouraging safety and efficacy data. However, randomized controlled trials will be necessary to confirm the role and positioning of CD19-directed CAR-T cells within the current MM treatment landscape.

We offer a strategy for deriving homogeneous and hypoimmunogenic CD19 CAR-iNK cells with robust anti-tumor effects from ESCs. Our study has significant implications for developing hypoimmunogenic CD19 CAR-NK cell therapy using human ESC as an unlimited cell source.

P1/2, N=81, Recruiting, University of Sao Paulo | Not yet recruiting --> Recruiting

P2, N=81, Terminated, Beijing Boren Hospital | Active, not recruiting --> Terminated; ethic commitee decision

CAR T therapy has been used with great success for human hematologic malignancies and is under development for use in canines. Our study is the first demonstration of functional feline CAR T cells and describes the procedures for their engineering. These findings lay the foundation for future development of CAR T therapy for multiple feline diseases.

P2, N=168, Active, not recruiting, Miltenyi Biomedicine GmbH | Trial completion date: Jul 2027 --> Jul 2029

Our data suggest that the CX3CR1/CX3CL1 axis is activated in CLL and may contribute to the NLC-driven growth-promoting effects of CLL cells. KAND567, which is in clinical trials in other disorders, should also be explored in CLL.

P2, N=72, Recruiting, Mayo Clinic | N=45 --> 72

Our findings underscore the importance of evaluating surface protein expression in HMCLs when modeling MM. The observed variations in expression levels emphasize the need for a strategic selection of cell lines based on the study's objectives.

P=N/A, N=15, Enrolling by invitation, Bioray Laboratories | Recruiting --> Enrolling by invitation

Mechanically, NKG7 preserved surface CAR expression and promoted CAR-T cell proliferation after exposing to relative tumor antigen. These results indicated that it may be feasible to explore single-cell sequencing data of clinical tumor samples to find strategies to improve CAR-T function, and that ectopic expression of NKG7 is an effective strategy to improve the therapeutic efficacy of CAR-T cells against tumors.

P=N/A, N=45, Not yet recruiting, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Conclusions : These findings underscore the significance of pre-treatment systemic inflammation (e.g. serum TNFa levels), product T cell phenotype, TMTV, CAR T-cell expansion, tumor IFN signaling and FLIPI as independent factors associated with clinical outcomes in patients with r/r FL treated with axi-cel. These results offer insights into mechanisms of resistance and toxicity, risk stratification, combination therapy and development of next-generation CAR-T therapy for patients with r/r FL.

Stem cell products with this T cell content will readily engraft into patients who have received lymphodepleting conditioning, yet despite this, we observed no unwanted engraftment, graft-versus-host disease, cytokine release syndrome after infusion of donor T cells, or enhanced toxicity of the blinatumomab. By demonstrating safety of infusion of large doses of unmodified donor lymphocytes, this study paves the way for future clinical trials of combinations of bispecific T cell engagers with allogeneic effector cells ('BiTEs plus cells').

We developed an OFRG-related signature to predict the prognosis and treatment responsiveness of individuals with GC and identified CDH19 as a possible therapeutic target for GC.

P1/2, N=24, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Jul 2024 --> Jul 2025

P2, N=300, Suspended, National Cancer Institute (NCI) | N=550 --> 300

P1, N=209, Recruiting, BioRay Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting | Phase classification: P1/2 --> P1

Importantly, although IL7/CD8 could promote T-cell proliferation, it did not sustain long-term autonomous expansion, which could ensure the safety of CD19 CAR-T cells expressing IL7/CD8 in clinical applications. Collectively, the IL7/CD8 construct represents a promising strategy for enhancing the therapeutic potential of CD19 CAR-T cell therapy.

This is the first report of B cell deficiency in 5 thymoma tissues of GS patients.

P1, N=28, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Jul 2025

P3; Initiation date: Jul 2024 --> Feb 2025

The results obtained in this study suggest that CXCR5 CD19 CAR-T cells should be investigated in a trial with broader patient populations.

P1/2, N=47, Recruiting, Juventas Cell Therapy Ltd. | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Jun 2024 --> Dec 2024

CAR-MNZ bearing the CD28-OX40-CD3ζ signaling modules, and CAR-BG2, designed on the Tisagenlecleucel CAR sequence (Kymriah®), carrying the 4-1BB and CD3ζ signaling elements, were employed. CIK + Blina displayed strongest NFAT and IFN-ɣ induction, whereas CARCIK-BG2 demonstrated superior synapse formation. All the effectors have shown therapeutic activity in vivo against the CD19+ Daudi tumor model, with CARCIK cells showing a more durable response compared to CIK + Blina, likely due to the short half-life of Blina in this model.

Lymphodepletion included fludarabine and cyclophosphamide The response was evaluated by bone marrow (BM) aspiration on day 28...Tocilizumab was administered to 2 patients and corticosteroids to 3 patients...However, the response is short and should be followed by allo-HSCT. Hopefully, future long term results will be improved by combining the CAR T- cell therapy with the emerging novel effective anti-leukemic compounds.

P2, N=86, Active, not recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Trial completion date: Sep 2025 --> Sep 2034

P2, N=29, Active, not recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Trial completion date: Oct 2028 --> Oct 2034

P2, N=106, Completed, University of Pennsylvania | Active, not recruiting --> Completed | Trial completion date: Aug 2024 --> Apr 2024 | Trial primary completion date: Aug 2024 --> Apr 2024

P=N/A, N=140, Not yet recruiting, Beijing GoBroad Hospital; Beijing GoBroad Hospital

P1, N=36, Recruiting, Sumithira Vasu | Trial completion date: Dec 2024 --> Jul 2026 | Trial primary completion date: Dec 2024 --> Apr 2025

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.