Views: 864 Author: Site Editor Publish Time: 2023-11-03 Origin: Site
The Annual Meeting of Society for Immunotherapy of Cancer (SITC) is the largest international event focusing on cancer immunotherapy in the world, attracting more than 3,500 participants each year from academia, regulatory authorities and government agencies. At this year's SITC Annual Meeting, which is being held in San Diego, USA, from November 1-5, Leads Biolabs published the preclinical data of anti-TNFR2 agonistic monoclonal antibody LBL-019 in the form of a poster.
LBL-019, a Novel TNFR2 Agonistic Antibody
Preferentially Activating CD8+ T Cells and Alleviating Tregs' Suppressive Effects
LBL-019 is a first-in-class TNFR2 agonistic monoclonal antibody, efficiently activating effector T cells to enhance their anti-tumor activity. Even in a high proportion of Regulatory T cells（Tregs）and T cell co-culture systems, LBL-019 can promote T cell proliferation and activation, counteracting the immunosuppressive effects of Tregs.
Poster Number: 841
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TNFR2 is highly expressed on activated T cells, particularly in tumor-infiltrating T cells. LBL-019 specifically binds to TNFR2, triggering downstream signaling, activating T cells, promoting T cell proliferation and cytokine release, exhibiting strong anti-tumor effects in murine tumor models.
In experimental systems simulating a tumor microenvironment (TME) with a high Treg ratio, LBL-019 retains its ability to activate T cells and alleviate Treg-mediated suppression of CD4+/CD8+ T cell proliferation.
During the process of T cell activation, LBL-019 upregulates PD-1 expression. Combining LBL-019 with a PD-1 antibody resulted in significant synergistic effect in both cellular experiments and murine tumor models. These findings offer compelling support for the potential clinical combination of PD-1 antibodies and LBL-019.
Currently, TNFR2 agonistic antibodies lack well-defined pharmacodynamic markers (PD markers). Our research has identified soluble TNFR2 (sTNFR2) as a potential PD marker. Preclinical investigations have demonstrated that LBL-019 can induce T cells to release sTNFR2. In studies testing LBL-019 in the MC38-hTNFR2 tumor model, there is a positive correlation between the concentration of sTNFR2 in serum and anti-tumor efficacy.
LBL-019 was granted clinical trial clearance by the Chinese National Medical Products Administration (NMPA) on December 10, 2021, and received IND approval from the U.S. Food and Drug Administration (FDA) on December 20, 2021. Currently, LBL-019 is undergoing Phase I clinical trials in China, and preliminary positive signals have already been demonstrated, indicating its potential as a best-in-class agent.
Dr. Hong Ling, Senior Vice President and Chief Scientific Officer of Leads Biolabs, introduced：LBL-019 is an agonistic monoclonal antibody targeting immune co-stimulatory molecule TNFR2 independently developed by Leads Biolabs and owned intellectual property rights. It has unique molecular characteristics and mechanisms，which can efficiently activate effector T cells with high selectivity and relieve the immunosuppressive effect of Tregs in the TME. Even in the experiment of simulating high proportion of Tregs infiltration in TME, LBL-019 can promote T cell proliferation and activation and play a powerful role in inhibiting the growth of tumor cells in animal experiments. With the development of clinical trials, it is expected to bring more treatment options and benefits to patients.
TNFR2 is selectively expressed in various immune cells, particularly in Tregs and activated T cells, promoting cell proliferation and activation. Two different types of TNFR2 antibodies are being developed internationally, targeting two distinct cell functions: clearance antibodies and agonistic antibodies. Clearance antibodies facilitate anti-tumor effects by clearing Tregs expressing TNFR2, but they carry the potential risk of depleting effector T cells and thereby weakening anti-tumor efficacy. Agonistic antibodies, on the other hand, activate and expand cytotoxic T cells to exert anti-tumor effects but may simultaneously activate Tregs, potentially diminishing their anti-tumor efficacy.
About Leads Biolabs
Nanjing Leads Biolabs Co., Ltd. is a clinical-stage biotechnology company founded in Nanjing by a team of senior U.S.-trained antibody drug developers. Since 2014, Leads Biolabs has been dedicated to the discovery and development of novel antibody drugs with independent intellectual property rights for the treatment of oncology and other major diseases of high unmet medical needs, particularly the challenges in cancer immunotherapy. Our extensive R&D pipeline consist of more than twenty novel tumor immunotherapy molecules based on monoclonal and bispecific antibody technology platforms. Leads Biolabs is committed to providing safe, effective, accessible and affordable new drugs to address the unmet needs of patients around the world.