A Phase 1, Open-Label Study to Evaluate the Safety and Tolerability of a Combination Autologous CD19 CAR T Cell Therapy (SYNCAR-001 + STK-009) in Subjects With Severe, Refractory Systemic Lupus Erythematosus

This is a phase 1 study of SYNCAR-001 + STK-009 in patients with severe, refractory systemic lupus erythematosus.

Start Date01 Sep 2024

Sponsor / Collaborator

Synthekine, Inc.Startup

NCT05665062 / RecruitingPhase 1

A Phase 1 Study to Evaluate the Safety and Tolerability of a Combination Autologous CD19 CAR T Cell Therapy (SYNCAR-001 + STK-009) in Subjects With Relapsed or Refractory CD19+ Hematologic Malignancies

This is a first-in-human phase 1 study of SYNCAR-001 + STK-009 in patients with CD19+ hematologic malignancies.

Start Date24 Jun 2022

Sponsor / Collaborator

Synthekine, Inc.Startup

100 Clinical Results associated with IL-2Rβ x CD19

100 Translational Medicine associated with IL-2Rβ x CD19

0 Patents (Medical) associated with IL-2Rβ x CD19

Literatures (Medical) associated with IL-2Rβ x CD19

01 Mar 2018·Nature MedicineQ1 · MEDICINE

A novel chimeric antigen receptor containing a JAK–STAT signaling domain mediates superior antitumor effects

Q1 · MEDICINE

Article

Author: Tanaka, Shinya ; Kagoya, Yuki ; Wang, Chung-Hsi ; Butler, Marcus O ; Anczurowski, Mark ; Saso, Kayoko ; Guo, Tingxi ; Minden, Mark D ; Hirano, Naoto

The adoptive transfer of T cells engineered with a chimeric antigen receptor (CAR) (hereafter referred to as CAR-T cells) specific for the B lymphocyte antigen CD19 has shown impressive clinical responses in patients with refractory B cell malignancies. However, the therapeutic effects of CAR-T cells that target other malignancies have not yet resulted in significant clinical benefit. Although inefficient tumor trafficking and various immunosuppressive mechanisms can impede CAR-T cell effector responses, the signals delivered by the current CAR constructs may still be insufficient to fully activate antitumor T cell functions. Optimal T cell activation and proliferation requires multiple signals, including T cell receptor (TCR) engagement (signal 1), co-stimulation (signal 2) and cytokine engagement (signal 3). However, CAR constructs currently being tested in the clinic contain a CD3z (TCR signaling) domain and co-stimulatory domain(s) but not a domain that transmits signal 3 (refs. 13, 14, 15, 16, 17, 18). Here we have developed a novel CAR construct capable of inducing cytokine signaling after antigen stimulation. This new-generation CD19 CAR encodes a truncated cytoplasmic domain from the interleukin (IL)-2 receptor β-chain (IL-2Rβ) and a STAT3-binding tyrosine-X-X-glutamine (YXXQ) motif, together with the TCR signaling (CD3z) and co-stimulatory (CD28) domains (hereafter referred to as 28-ΔIL2RB-z(YXXQ)). The 28-ΔIL2RB-z(YXXQ) CAR-T cells showed antigen-dependent activation of the JAK kinase and of the STAT3 and STAT5 transcription factors signaling pathways, which promoted their proliferation and prevented terminal differentiation in vitro. The 28-ΔIL2RB-z(YXXQ) CAR-T cells demonstrated superior in vivo persistence and antitumor effects in models of liquid and solid tumors as compared with CAR-T cells expressing a CD28 or 4-1BB co-stimulatory domain alone. Taken together, these results suggest that our new-generation CAR has the potential to demonstrate superior antitumor effects with minimal toxicity in the clinic and that clinical translation of this novel CAR is warranted.

01 Oct 2017·Metabolic Brain DiseaseQ3 · MEDICINE

Estrogen protects both sexes against EAE by promoting common regulatory cell subtypes independent of endogenous estrogen

Q3 · MEDICINE

Article

Author: Vandenbark, Arthur A ; Offner, Halina ; Nguyen, Ha ; Benedek, Gil ; Seifert, Hilary A ; Kent, Gail

Autoimmune diseases including multiple sclerosis predominantly affect females. Although high levels of sex hormones, particularly estrogen (E2), can reduce proinflammatory immune responses, it remains unclear if a lack of endogenous sex hormones might affect treatment with exogenous sex hormones. Pretreatment with E2 almost completely prevents intact female and male mice from developing clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) by promoting various regulatory immune cell phenotypes. To evaluate the effects of exogenous estrogen in the absence of endogenous sex hormones, the current study compared EAE severity and the emergence of different immunoregulatory cell populations after E2 pretreatment of ovariectomized (OVX) female versus male mice. We found that E2 equally protected both OVX females and males from EAE over a 21 day observation period concomitant with reduced total cell numbers in spleen and spinal cord (males only), but enhanced percentages of CD19⁺CD5⁺CD1d^hi, CD19⁺CD138⁺CD44^hi and CD19⁺Tim-1⁺ Breg cells, CD8⁺CD122⁺ Treg cells and CD11b⁺CD 206⁺ARG-1⁺ anti-inflammatory M2-like monocytes/macrophages in both groups. In contrast, E2 decreased the percentage of CD4⁺CD25⁺FoxP3⁺ Treg cells in OVX females but increased these Treg cells in males and intact female mice. These data suggest that with the exception of CD4⁺CD25⁺FoxP3⁺ Treg cells, E2 protection against EAE promotes highly overlapping immunoregulatory subsets in OVX females and males.

01 Jun 2014·Zhongguo shi yan xue ye xue za zhi

[Expression of CD25 in acute B cell lymphoblastic leukemia and its clinical significance].

Article

Author: Zhang, Yao-Fang ; Hou, Yan-Fei ; Yang, Lin-Hua ; Ren, Fang-Gang ; Wang, Mei-Fang ; Zhang, Rui-Juan ; Ge, Xiao-Yan ; Wang, Yun-Peng ; Yang, Chen

This study was purposed to investigate the relation of CD25 with the acute B cell lymphoblastic leukemia (B-ALL) and its clinical significance. A totol of 88 newly diagnosed B-ALL patients were enrolled in this study. The immunophenotype of leukemic myeloblasts were detected by flow cytometry, including interleukin 2 receptor α chain (CD25), β chain (CD122), γ chain (CD132), CD19, CD20, CD10, CD34, CDIgM, CD79a, CD22 and CDTDT. The expression of BCR/ABL fusion gene was detected by qualitative PCR. The expression of IL2RA (CD25 gene) was detected by real-time qualitative RT-PCR. The results showed that there was no significant statistical difference in WBC count, Hb level, PLT count, marrow blast rate, peripheral blast rate, hepato-lienal infiltration, lymph node infiltration, levels of CD10, CD20, CD22, CD34, CD79a, CDTDT, CDIgM expression between B-ALL patients with CD25(+) and B-ALL patients with CD25(-), while the CD19 expression level in B-ALL patients with CD25(+) was higher than that in B-ALL patients with CD25(-). Out of 88 B-ALL patients, 21 patients showed BCR/ABL(+)(21/88) and their CD25(+) expression level was 66.7% (14/21); 67 patients showed BCR/ABL(-) and their CD25(+) expression level was 4.5% (3/67), there was statistical difference between these two groups (P < 0.05), but the expression level of IL2RA mRNA was not statistical different between CD25(+) and CD25(-) groups (P > 0.05). Among 21 BCR/ABL(+) B-ALL patients the remission rate and relapsed rate were not statistical different between CD25(+) an CD25(-) groups.In BCR/ABL(+) B-ALL patients 8 patients relapsed, the relapsed rate was 38.1% (8/21). In BCR/ABL(-) B-ALL patients 9 patients relapsed, the relapse rate was 13.4% (9/67), there was statistical difference between BCR/ABL(+) and BCR/ABL(-) two groups (P < 0.05). In BCR/ABL(+) group the RFS (relapse free survival) was 21 months, in BCR/ABL(+) CD25(+) patients the RFS was 15 months, while in BCR/ABL(+) CD25(-) patients the RFS was 21 months, in BCR/ABL(-) CD25(-) patients, the RFS was 24 months. It is concluded that the CD25 expresses at high level in B-ALL patients with BCR/ABL(+), which may serve as a predictive marker for the presence of BCR/ABL fusion gene, and relates with relapse, CD25(+) may serve as a adjuvant indicator for poor prognosis.

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