Request Demo

Last update 08 May 2025

RAET1G

Last update 08 May 2025

Basic Info

Synonyms

RAET1G, retinoic acid early transcript 1G, Retinoic acid early transcript 1G protein

+ [2]

Introduction

Binds and activates the KLRK1/NKG2D receptor, mediating natural killer cell cytotoxicity. Down-regulates the expression of KLRK1 and stimulates natural killer cells to secrete IFNG. Stimulates natural killer cells to secrete IFNG.

Drugs associated with RAET1G

EVOLVE-104

Target

CD2 x CD3 x RAET1G x RAET1L x ULBP2

Mechanism

CD2 agonists [+6]

Active Org.

Evolveimmune Therapeutics, Inc.

Originator Org.

Evolveimmune Therapeutics, Inc.

Active Indication

Squamous Cell Neoplasms [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with RAET1G

100 Translational Medicine associated with RAET1G

0 Patents (Medical) associated with RAET1G

Literatures (Medical) associated with RAET1G

01 Mar 2025·Cancer Research Communications

23ME-01473, an Fc Effector–Enhanced Anti-ULBP6/2/5 Antibody, Restores NK Cell–Mediated Antitumor Immunity through NKG2D and FcγRIIIa Activation

Article

Author: Ayupova, Dina ; Fuh, Germaine ; Ivic, Nives ; Tilk, Susanne ; Diep, Anh N. ; Gerrick, Kimberline Y. ; Bahrami Dizicheh, Zahra ; Kellar, Danielle ; Benjamin, Joel S. ; Shi, Shi ; Chen, I-Ling ; Bonnans, Caroline ; Hom, Clifford ; Bharill, Shashank ; Schmidt, Maike ; Poggio, Mauro ; Fontanillas, Pierre ; Sood, Pranidhi ; Yadav, Shruti ; Sen, Debasish ; Koenig, Patrick ; Jarret, Abigail ; Owyang, Alex

AbstractThe landscape of cancer treatment has been transformed by immune checkpoint inhibitors; however, the failure to benefit a large number of patients with cancer has underlined the need to identify promising targets for more effective interventions. In this study, we leverage 23andMe, Inc.’s large-scale human germline genetic and health database to uncover the previously unknown role of UL16-binding protein 6 (ULBP6), a high-affinity NK group 2D (NKG2D) ligand, in cancer and its promise as an immuno-oncology therapeutic target. We confirm ULBP6 expression in human tumors and demonstrate that soluble ULBP6 shed from tumors circumvents NKG2D activation provided by membrane-anchored NKG2D ligands to inhibit immune cell activation and tumor cell killing. Based on these findings, we developed 23ME-01473, a humanized Fc effector–enhanced antibody that binds to ULBP6 and its closely related family members, ULBP2 and ULBP5. 23ME-01473 effectively blocks soluble ULBP6-mediated immunosuppression to restore the NKG2D axis on NK and T cells to elicit tumor growth control. Moreover, the Fc effector–enhanced design of 23ME-01473 increases its binding affinity to fragment crystallizable gamma receptor IIIa, which, together with 23ME-01473’s binding to membrane-anchored ULBP6/2/5 on cancer cells, allows for augmented antibody-dependent cellular cytotoxicity induction, providing a second activation node for NK cells. Our studies demonstrate the therapeutic potential of an Fc effector–enhanced anti-ULBP6/2/5 antibody to reinvigorate NK cell and T-cell activation and cytotoxicity for the treatment of cancer.Significance:This study emphasizes the utility of population-based genome-wide assessments for discovering naturally occurring genetic variants associated with lifetime risks for cancer or immune diseases as novel drug targets. We identify ULBP6 as a potential keystone member of the NKG2D pathway, which is important for antitumor immunity. Targeting ULBP6 may hold therapeutic promise for patients with cancer.

01 Mar 2023·Cancer Medicine

A signature based on NKG2D ligands to predict the recurrence of hepatocellular carcinoma after radical resection

Article

Author: Chen, Pu ; Liao, Weijia ; She, Shaoping ; Chen, Dongbo ; Chen, Hongsong ; Gao, Jie ; Xie, Yong ; Ren, Liying ; Yang, Yao

AbstractIntroductionDue to the high recurrence, the HCC prognosis remains poor. Yet, the biomarkers for predicting the recurrence of high‐risk patients are currently lacking. We aimed to develop a signature to predict the recurrence of HCC based on NKG2D ligands.MethodsThe multivariate Cox proportional hazards regression was used to select recurrence‐related variables of NKG2D ligands in HCC patients from The Cancer Genome Atlas (TCGA). HCC patients from the OEP000321 dataset and Guilin cohort were used to validate the predictive signature. The mRNA expression of NKG2D ligands was measured by QRT‐PCR. Immunohistochemistry analysis of HCC tissue microarray samples was used to identify the expression of NKG2D ligands.ResultsIn this study, NKG2D ligands expression in the mRNA and protein level was both abnormally expressed in HCC and associated with recurrence‐free survival (RFS). Then, the recurrence‐related variables of NKG2D ligands in HCC were selected by the multivariate Cox proportional hazards regression. Among the eight NKG2D ligands, MICA (HR = 1.347; 95% CI = 1.012–1.793; p = 0.041), ULBP3 (HR = 0.453; 95% CI = 0.231–0.889; p = 0.021) and ULBP5 (HR = 3.617; 95% CI = 1.819–7.194; p < 0.001) were significantly correlated with RFS in the TCGA‐LIHC cohort. Then, the signature was constructed by the three NKG2D ligands. The predictive effectiveness of this signature was also validated in the OEP000321 dataset and Guilin cohort. Further, HCC patients were classified into low‐risk and high‐risk subgroups by the predictive score. Compared with the low‐risk group, the high‐risk group had poor RFS in both training and validation cohorts. Importantly, compared with the low‐risk patients with the G1‐G2 stage, the levels of infiltrated NK‐activated cells and NKG2D expression were both lower in the high‐risk patients.ConclusionsThe signature based on MICA, ULBP3, and ULBP5 could predict HCC recurrence.

01 Apr 2020·The Journal of ImmunologyQ2 · MEDICINE

Fumarate Upregulates Surface Expression of ULBP2/ULBP5 by Scavenging Glutathione Antioxidant Capacity

Q2 · MEDICINE

Article

Author: Mellergaard, Maiken ; Møller, Sofie Hedlund ; Andresen, Lars ; Høgh, Rikke Illum ; Jepsen, Stine Dam ; Droujinine, Alec ; Skov, Søren

AbstractFumarate is a tricarboxylic acid cycle metabolite whose intracellular accumulation is linked to inflammatory signaling and development of cancer. In this study, we demonstrate that endogenous fumarate accumulation upregulates surface expression of the immune stimulatory NK group 2, member D (NKG2D) ligands ULBP2 and ULBP5. In agreement with this, accumulation of fumarate by the therapeutic drug dimethyl fumarate (DMF) also promotes ULBP2/5 surface expression. Mechanistically, we found that the increased ULBP2/5 expression was dependent on oxidative stress and the antioxidants N-acetylcysteine and glutathione (GSH) abrogated ULBP2/5 upregulated by DMF. Fumarate can complex with GSH and thereby exhaust cells of functional GSH capacity. In line with this, inhibition of GSH reductase (GR), the enzyme responsible for GSH recycling, promoted ULBP2/5 surface expression. Loss of the tricarboxylic acid cycle enzyme fumarate hydratase (FH) associates with a malignant form of renal cancer characterized by fumarate accumulation and increased production of reactive oxygen species, highlighting fumarate as an oncometabolite. Interestingly, FH-deficient renal cancer cells had low surface expression of ULBP2/5 and were unresponsive to DMF treatment, suggesting that the fumarate-stimulating ULBP2/5 pathway is abrogated in these cells as an immune-evasive strategy. Together, our data show that ULBP2/5 expression can be upregulated by accumulation of fumarate, likely by depleting cells of GSH antioxidant capacity. Given that DMF is an approved human therapeutic drug, our findings support a broader use of DMF in treatment of cancers and inflammatory conditions.

News (Medical) associated with RAET1G

23 Oct 2024

·www.globenewswire.com

EvolveImmune Therapeutics to Present New Preclinical Data Highlighting Pipeline Progress for EVOLVE T Cell Engager Platform at 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC)

Multiple Presentations on Lead Development Candidate EVOLVE104 to Showcase Preclinical Safety and Efficacy Profile and Precision Therapeutic Strategy as Company Advances Program Toward Clinic for Solid Tumors Unveiling of CD20-Targeted EVOLVE205 Demonstrates Expanded EVOLVE Platform Development Offering a Differentiated Strategy for Hematologic Tumors BRANFORD, Conn., Oct. 23, 2024 (GLOBE NEWSWIRE) -- EvolveImmune Therapeutics, an immuno-oncology company developing first-in-category, multifunctional biotherapeutics to overcome the therapeutic challenges of cancer cell resistance to current immune therapy agents, today announced that new preclinical data highlighting EVOLVE, the company’s novel costimulatory T cell engager platform, will be presented at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), which is being held November 6-10, 2024, in Houston, Texas. The poster presentations will include the latest preclinical results for the company’s lead development candidate, EVOLVE104, being developed for the treatment of solid tumors. Additionally, the company will spotlight work designed to expand the potential of the EVOLVE platform by applying integrated CD2 co-stimulation to next-generation T cell engager formats. The EVOLVE platform uniquely unleashes potent, selective and integrated T cell co-stimulation, which amplifies and sustains the tumor killing capacity of these T cells. This approach bypasses low tumor immunogenicity, conditionally activates adaptive immunity and reduces T cell dysfunction to overcome therapeutic challenges in solid and hematologic tumors. By pairing its distinctive co-stimulation strategy with EvolveImmune’s deep insights in cancer cell biology, EVOLVE enables the discovery and development of first-in-category precision immuno-oncology agents with an enhanced likelihood of clinical success. In two poster presentations, EvolveImmune will highlight the latest preclinical safety and efficacy data for EVOLVE104, a novel multi-functional T cell engager with integrated CD2 co-stimulation which conditionally targets ULBP2/5/6. This will include evidence of a favorable safety and tolerability profile, and updated ULBP2/5/6 RNA and immunohistochemistry analyses across a range of solid tumor types to pinpoint cancers enriched for its expression and most likely to respond to EVOLVE104 therapy. Importantly, the expression pattern for ULBP2/5/6 suggests opportunities to clinically differentiate EVOLVE104 from several approved or investigational immunotherapies. EvolveImmune continues to progress its chemistry, manufacturing, and control (CMC) activities for EVOLVE104, with the goal of advancing the program into the clinic in 2025. In addition, the company will deliver an oral presentation highlighting the discovery and profiling of EVOLVE205, a highly potent CD20-targeted CD2 co-stimulatory T cell engager designed in a 2:1 bispecific format. Presented data will include promising initial preclinical activity for EVOLVE205, findings which demonstrate both its potential differentiation from approved CD20-targeted immunotherapies and the growing capability of the EVOLVE platform to serve as a backbone for emerging classes of T cell engager therapies. “The upcoming SITC conference offers an ideal forum for us to share our significant pipeline progress not only with EVOLVE104 but also our success in unlocking the broad potential of the EVOLVE platform to enable the design of next-generation T cell engagers capable of overcoming therapeutic limitations of current immuno-oncology treatments,” said Jay Fine, Ph.D., president of research and development at EvolveImmune. “Our robust preclinical work on EVOLVE104 continues to build optimism for the clinical potential of the program, and we look forward to completing IND-enabling activities and advancing the compound into first-in-human studies in the coming year. At the same time, our excitement around our foundational EVOLVE technology and its fully integrated CD2 co-stimulation has never been greater.” Details of the company’s SITC presentations are as follows: EVOLVE104 Poster Presentations: Title: EVOLVE104, a first-in-class novel ULBP2/5/6-targeting T cell engager with integrated CD2 co-stimulation, demonstrates a favorable preclinical safety and toxicity profile in cynomolgus monkeysAbstract Number: 1339Presenter: Antonio Ward, Ph.D.Session: Novel Single-Agent ImmunotherapiesSession Date/Time: Friday, November 8, 2024 from 9:00 a.m. – 7:00 p.m. CSTLocation: Poster Hall in Exhibit Halls A and B of the George R. Brown Convention Center Title: Precision oncology strategy for EVOLVE-104, a differentiated T cell engager for the novel solid tumor target ULBP2/5/6Abstract Number: 1326Presenter: Oksana Sergeeva, Ph.D.Session: Novel Single-Agent ImmunotherapiesSession Date/Time: Friday, November 8, 2024 from 9:00 a.m. – 7:00 p.m. CSTLocation: Poster Hall in Exhibit Halls A and B of the George R. Brown Convention Center EVOLVE205 Oral Presentation: Title: EVOLVE205, a highly potent 2:1 CD20-targeted CD2 co-stimulatory T cell engager engineered for the treatment of B cell malignancies and B cell autoimmune diseasesAbstract Number: 1137Presenter: Afsana Sabrin, Ph.D.Session: CAR-T Cells vs T-cell Engineering Bispecifics in Hematological MalignanciesSession Date/Time: Saturday, November 9, 2024 from 5:15 -6:35 p.m. CSTLocation: Level 3 - Grand Ballroom A of the George R. Brown Convention Center The EVOLVE205 presentation will also be included in the poster session at the pre-conference Immune Engineering Workshop on Thursday, November 7, as well as during the poster reception on Friday, November 8. Additional information on the 39th Annual Meeting of SITC is available through the conference website at: https://www.sitcancer.org/2024/home About EvolveImmune Therapeutics EvolveImmune Therapeutics, Inc. is an immunotherapy platform company developing first-in-category, multifunctional biotherapeutics designed to overcome cancer-driven immunodeficiency in a range of solid tumors and hematological cancers. First-in-human clinical trials are anticipated in 2025. The company is supported by a syndicate of top-tier life science industry investors including Pfizer Ventures, Solasta Ventures, Bristol Myers Squibb, Takeda Ventures, Inc., Yonjin Ventures and Elm Street Ventures. For more information, please visit: www.evolveimmune.com

ImmunotherapyAACRClinical Study

Analysis

Perform a panoramic analysis of this field.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

RAET1G

Basic Info

Related

Analysis