SUZHOU, China, Apr.18, 2023, Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, has presented two preclinical study results of TST003, a First-in-Class mAb Targeting GREMLIN-1, and TST010, an ADCC enhanced anti-CD25 mAb as posters at the American Association for Cancer Research (AACR) Annual Meeting 2023. The full text of posters is available on Transcenta's website: https://www.transcenta.com/news/Industry_News
The details of posters are as follows:
Title: The Preclinical Characterization of TST003, a First-in-Class mAb Targeting GREMLIN-1 Overexpressed by Cancer-Associated Fibroblasts and Tumor Cells
Abstract#: 465
Session Date and Time: Sunday Apr 16, 2023 1:30 PM - 5:00 PM (EDT)
Cancer associated fibroblast (CAF) is a rich source of factors for immune suppression and promotes cancer progression and metastasis via epithelial to mesenchymal transition (EMT). It is well known that tumors with mesenchymal phenotype have significantly poor prognosis and reduced response to checkpoint inhibitors. Targeting CAF becomes an increasingly attractive cancer therapeutic approach. Gremlin-1 is a member of the TGFβ superfamily, expressed by CAFs and tumor cells, and known to play a key role in EMT transition, cancer cell proliferation and stroma maintenance. Gremlin-1 overexpression in CAF or tumor cells often correlates with poor clinical prognosis in multiple cancers including colorectal, prostate, pancreatic, gastric and lung cancer etc.
Preclinical characterization results provided the rationale for on-going clinical evaluation of TST003 in patients with advanced solid tumors with high unmet medical need either as monotherapy or in combination with SoC.
Title: ADCC enhanced anti-CD25 mAb (TST010) exhibited potent anti-tumor activity by depleting Treg cells and increasing CD8+T/Treg ratio in preclinical tumor models
Abstract#: 1546
Session Time: Monday Apr 17, 2023 9:00 AM - 12:30 PM (EDT)
Regulatory T (Treg) cells are a distinctive lineage of CD4+ T cells characterized by the expression of FoxP3 and CD25 markers. Treg cells are involved in tumor development and progression by inhibiting anti-tumor immunity. Accumulation of Treg cells in the tumor microenvironment (TME) is often associated with an adverse prognosis in multiple cancers and also has implication for predicting response to immunotherapy. Treg cell depletion strategy has been explored in preclinical and clinical settings to induce effective anti-tumor immune responses in TME. CD25, a high-affinity binding subunit alpha of the IL-2 receptor, is constitutively and highly expressed on Treg cells but also transiently upregulated on effector T cells. The high level of CD25 expression on Treg cells could deprive of IL-2 for effector T cells and inhibit their proliferation. Thus, an effective approach to selectively suppress Treg cell function is to deplete Treg cells while avoid blocking IL-2 binding to CD25 for allowing T effect cell proliferation and activation.
Preclinical tumor models demonstrate that TST010 has a good potential to induce effective anti-tumor immune responses in TME and tumor growth inhibition especially in combination with PD-1/PD-L1 inhibitor.
About TST003
TST003 is a high affinity monoclonal antibody targeting Gremlin1, a member of the TGF-βsuperfamily. Gremlin1 protein is a highly conserved secreted protein and has shown to play important roles during embryonic development and promote epithelial mesenchymal transition. Gremlin1 is upregulated in multiple solid tumors. TST003 has demonstrated promising single agent and combination activities in patient-derived xenograft tumor models from the difficult-to-treat solid tumors resistant to checkpoint inhibitors including castration resistant prostate cancer and microsatellite stable colorectal cancer.
About TST010
Using immune tolerance breaking antibody platform, Transcenta generated a humanized IgG1 subtype anti-CD25 monoclonal antibody with reduced fucose (TST010). TST010 binds to human CD25 with high affinity and selectivity, but does not block IL-2 binding to CD25. Non-blocking activity to IL-2 signaling on human PBMC has been further confirmed by the phosphorylation of STAT5. By reducing fucosylation during cell culture process, TST010 mAb gains the enhanced ADCC activity in vitro and anti-tumor activity by depleting Treg cells and increasing CD8+T/Treg ratio in preclinical tumor models.
About Transcenta Holding Limited
Transcenta (HKEX: 06628) is a clinical stage biopharmaceutical company with fully integrated capabilities in antibody-based biotherapeutics discovery, research, development and manufacturing.
Transcenta has established global footprint, with Headquarters and Discovery, Clinical and Translational Research Center in Suzhou, Process and Product Development Center and Manufacturing Facility in Hangzhou, and Clinical Development Centers in Princeton, US and in Beijing, Shanghai and Guangzhou of China, and External Partnering Center in Boston and Los Angeles, US. Transcenta has also initiated the construction of the Group Headquarters and the second high-end biopharmaceutical facility with ICB as its core technology in Suzhou Industrial Park. Transcenta is developing ten therapeutic antibody molecules for oncology and selected non-oncology indications including bone and kidney disorders.
For more information, please visit www.transcenta.com and https://www.linkedin.com/company/transcenta.
Original source can be found here.
