Last update 01 Nov 2024

IL2RA x CD73

Last update 01 Nov 2024

Basic Info

Related Targets

IL2RACD73

Drugs associated with IL2RA x CD73

GI-108

Target

CD73 x IL2RA

Mechanism

CD73 inhibitors [+1]

Active Org.

GI Innovation, Inc.

Originator Org.

GI Innovation, Inc.

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with IL2RA x CD73

100 Translational Medicine associated with IL2RA x CD73

0 Patents (Medical) associated with IL2RA x CD73

104

Literatures (Medical) associated with IL2RA x CD73

31 Dec 2024·Hematology

Dioscin alleviates aplastic anemia through regulatory T cells promotion

Article

Author: Wang, Aidi ; Liu, Baoshan ; Zhang, Le ; Fan, Liwei ; Wang, Haijin ; Ni, Runfeng

Objectives: Aplastic anemia (AA) is one of the immune-mediated bone marrow failure disorders caused by multiple factors, including the inability of CD4 + CD25 + regulatory T cells (Tregs) to negatively regulate cytotoxic T lymphocytes (CTLs). Dioscin is a natural steroid saponin that has a similar structure to steroid hormones. The purpose of this study is to look into the effect of Dioscin on the functions of CD4 + CD25+ Tregs in the AA mouse model and explore its underlying mechanism.Methods: To begin with, bone marrow failure was induced through total body irradiation and allogeneic lymphocyte infusion using male Balb/c mice. After 14 consecutive days of Dioscin orally administrated, the AA mouse model was tested for complete blood counts, HE Staining of the femur, Foxp3, IL-10 and TGF-β. Then CD4 + CD25+ Tregs were isolated from splenic lymphocytes of the AA mouse model, Tregs and the biomarkers and cytokines of Tregs were measured after 24 h of Dioscin intervention treatment in vitro.Results: Dioscin promotes the expression of Foxp3, IL-10, IL-35 and TGF-β, indicating its Tregs-promoting properties. Mechanistically, the administration of Dioscin resulted in the alteration of CD152, CD357, Perforin and CD73 on the surface of Tregs, and restored the expression of Foxp3.Conclusion: Dioscin markedly attenuated bone marrow failure, and promoted Tregs differentiation, suggesting the maintenance of theimmune balance effect of Dioscin. Dioscin attenuates pancytopenia and bone marrow failure via its Tregs promotion properties.

31 Dec 2024·OncoImmunology

Expression of CD39 is associated with T cell exhaustion in ovarian cancer and its blockade reverts T cell dysfunction

Article

Author: Seubert, Elisa ; Koch-Nolte, Friedrich ; Qi, Minyue ; Wellbrock, Jasmin ; Witt, Marius ; Schmalfeldt, Barbara ; Menzel, Stephan ; Brauneck, Franziska ; Sturmheit, Tabea ; Weimer, Pauline ; Bokemeyer, Carsten ; Ding, Yi ; Fiedler, Walter ; Hell, Louisa ; Oliveira-Ferrer, Leticia

Immune exhaustion is a hallmark of ovarian cancer. Using multiparametric flow cytometry, the study aimed to analyze protein expression of novel immunological targets on CD3⁺ T cells isolated from the peripheral blood (n = 20), malignant ascites (n = 16), and tumor tissue (n = 6) of patients with ovarian cancer (OVCA). The study revealed an increased proportion of effector memory CD8⁺ T cells in OVCA tissue and malignant ascites. An OVCA-characteristic PD-1^high CD8⁺ T cell population was detected, which differed from PD-1^lowCD8⁺ T cells by increased co-expression of TIGIT, CD39, and HLA-DR. In addition, these OVCA-characteristic CD8⁺ T cells showed reduced expression of the transcription factor TCF-1, which may also indicate reduced effector function and memory formation. On the contrary, the transcription factor TOX, which significantly regulates terminal T cell-exhaustion, was found more frequently in these cells. Further protein and gene analysis showed that CD39 and CD73 were also expressed on OVCA tumor cells isolated from solid tumors (n = 14) and malignant ascites (n = 9). In the latter compartment, CD39 and CD73 were also associated with the expression of the "don't eat me" molecule CD24 on tumor cells. Additionally, ascites-derived CD24⁺EpCAM⁺ tumor cells showed a higher frequency of CD39⁺ or CD73⁺ cells. Furthermore, CD39 expression was associated with unfavorable clinical parameters. Expression of CD39 on T cells was upregulated through CD3/CD28 stimulation and its blockade by a newly developed nanobody construct resulted in increased proliferation (eFluor), activation (CD25 and CD134), and production of cytotoxic cytokines (IFN-γ, TNF-α, and granzyme-B) of CD8⁺ T cells.

10 Oct 2024·Blood

Mitigation of checkpoint inhibitor–induced autoimmune hemolytic anemia through modulation of purinergic signaling

Article

Author: Fliginger, Daysha ; Panch, Sandhya ; Jagnarine, Shwatina ; Hudson, Krystalyn E. ; Stone, Elizabeth F. ; Kyritsis, Emmalene ; D’Agati, Vivette D. ; Qiu, Annie ; Miller, Anabel ; Dei Zotti, Flavia ; Tredicine, Maria

AbstractImmune checkpoint inhibitors (ICPis) have revolutionized cancer immunotherapy but also can induce autoimmune hemolytic anemia (AIHA), a severe disease with high mortality. However, the cellular and molecular mechanism(s) of AIHA secondary to ICPi therapy (ICPi-AIHA) are unclear, other than being initiated through decreased checkpoint inhibition. Herein, we report ICPi-AIHA in a novel mouse model that shows similar characteristics of known human ICPi-AIHA (eg, autoantibodies, hemolysis, and increased mortality). During ICPi-AIHA, there is the simultaneous reduction of 2 regulatory T-cell populations (FoxP3+ and Tr1 [type 1 regulatory cells]) and an increase in inflammatory T helper cell 17 (TH17). Moreover, a novel CD39+CD73–FoxP3–CD25– CD4+ T-cell subset (ie, CD39 single positive [CD39SP]) emerges, and early increases in CD39SP predict AIHA development; CD39 is an ectonuclease that breaks down adenosine triphosphate (ATP). Additionally, we found that boosting ATPase activity by injecting recombinant apyrase mitigates AIHA development and significant CD39SP reductions, both suggesting a functional role for CD39 and demonstrating a novel therapeutic approach. Importantly, CD39SP are detectable in multiple mouse models developing AIHA and in patients with AIHA, demonstrating applicability to idiopathic and secondary AIHA. Highlighting broader autoimmunity relevance, ICPi-treated NZB mice experienced accelerated onset and severity of lupus, including AIHA. Moreover, ICPi treatment of healthy B6 animals led to detectable CD39SP and development of autoantibodies against multiple autoantigens including those on red blood cells and platelets. Together, our findings provide further insight into the cellular and molecular mechanisms of ICPi-AIHA, leading to novel diagnostic and therapeutic approaches with translational potential for use in humans being treated with ICPi.

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