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PA007169.m1DA: 体内实验级重组抗小鼠GITR单克隆抗体（克隆号DTA-1），小鼠IgG1-D265A Lambda（In Vivo Grade Recombinant Anti-mouse GITR Mouse IgG1-D265A Lambda Monoclonal Antibody （Clone DTA-1））

大鼠抗小鼠 GITR 单克隆抗体 DTA-1（大鼠 IgG2b lambda）可与小鼠 GITR 蛋白（糖皮质激素诱导的 TNFR 相关蛋白，即肿瘤坏死因子受体 (TNFR) 超家族 18，TNFRSF18）发生反应。DTA-1 单克隆抗体特异性结合的小鼠 GITR 主要表达于 CD4+CD25+ 调节性 T 细胞（Treg）以及 CD25+ CD4+ CD8- 胸腺细胞表面。

我们的重组 DTA-1 抗体包含大鼠抗小鼠 GITR 单克隆抗体（杂交瘤克隆名称或编号：DTA-1）的部分（可变区）或完整氨基酸序列。

抗小鼠 GITR 单克隆抗体（克隆号：DTA-1）参考文献：

1. Rational design of anti-GITR-based combination immunotherapy.

Zappasodi, et al. Nat Med. 2019 May;25(5):759-766. PMID: 31011209

“Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) is a promising target for cancer immunotherapy. … Here, we demonstrate that the anti-tumor efficacy of GITR agonism relies on the reduction of intra-tumoral regulatory T (Treg) cells and the activation of CD8+ T cells. … These findings provide a mechanistic rationale for combining anti-GITR with anti-PD-1 or anti-CTLA-4 to overcome resistance to immune checkpoint blockade.”

2. Local Administration of GITR Agonistic Antibody Induces a Stronger Antitumor Immunity than Systemic Delivery.

Wang, et al. Front Immunol. 2019 Mar 20;10:486. PMID: 30949170

“Agonistic antibodies targeting the glucocorticoid-induced TNFR-related protein (GITR) have shown promise in preclinical tumor models. … In this study, we demonstrate that local administration of an anti-GITR agonistic antibody (DTA-1) elicits superior antitumor immunity compared to systemic delivery. … The enhanced efficacy of local delivery is associated with increased depletion of regulatory T cells and robust activation of tumor-infiltrating effector T cells in the tumor microenvironment.”

3. Therapeutic antibody activation of the glucocorticoid-induced TNF receptor by a clustering mechanism.

Zhang, et al. Cell Rep. 2022 Feb 22;38(8):110427. PMID: 35196495

“The glucocorticoid-induced TNF receptor (GITR) is a costimulatory immune checkpoint molecule that enhances T cell responses when activated by agonistic antibodies. … Our study reveals that therapeutic anti-GITR antibodies require Fc-gamma receptor (FcγR)-mediated cross-linking to effectively cluster GITR and trigger optimal downstream signaling. … These insights highlight the critical role of antibody clustering mechanisms and provide a framework for engineering next-generation GITR-targeted immunotherapeutics.”

4. Th2 responses to helminth parasites can be therapeutically enhanced by, but are not dependent upon, GITR-GITRL co-stimulation in vivo.

Nair, et al. Infect Immun. 2012 Oct;80(10):3454-3463. PMID: 22825447

“The glucocorticoid-induced tumor necrosis factor receptor (GITR) and its ligand (GITRL) play critical roles in regulating both innate and adaptive immune responses. … Here we investigated the requirement for GITR-GITRL interactions in the development of Th2 immunity against helminth parasites using in vivo murine models. … We found that while endogenous GITR signaling is not strictly required for initiating Th2 responses, therapeutic engagement of GITR using an agonistic antibody can significantly enhance parasite clearance and Th2 cytokine production.”

5. Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy.

Yang, et al. Nat Commun. 2021 Feb 5;12(1):832. PMID: 33547300

“Galectin-9 (Gal-9) is a widely expressed mammalian lectin that plays a crucial role in immune tolerance and T cell exhaustion within the tumor microenvironment. … We demonstrate that Gal-9 binds directly to both PD-1 and TIM-3, forming a complex that promotes apoptosis in effector T cells and facilitates tumor immune evasion. … Blockade or modulation of this Gal-9 network, potentially in combination with other immune checkpoint regulators like GITR or PD-L1, represents a promising strategy for synergistic cancer immunotherapy.”

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