GRÍFOLS / GIGAGEN INC . En el Festival Of Biológics USA Que se Celebrará en San Diego El 20 de Marzo se Presentarán Estos Resultados en Donde Sorprendentemente, GIGA-564 ( By GIGAGEN INC / GRIFOLS ) Tiene una Actividad Antitumoral Superior en Comparación con YERVOY ( IPILIMUMAB BY BRISTOL MYERS ) en un Modelo Murino .

GIGA-564, a Third-Generation Anti-CTLA-4, Has Enhanced Efficacy But Reduced Toxicity Compared To IPILIMUMAB in PRE-CLINICAL MODELS  .

Checkpoint Inhibitors .

Anti-CTLA-4 Antibodies Such as IPILIMUMAB Were Among The First Immune-Oncology Agents To Show Significantly Improved Outcomes For Patients .

 However, existing anti-CTLA-4 Therapies Fail to induce a Response in a Majority of Patients and can Induce Severe, Immune-Related Adverse Events .

 

It Has Neen Assumed that Checkpoint inhibition, i.e., Blocking The Interaction Between CTLA-4 and Its Ligands, is The Primary Mechanism of Action For IPILIMUMAB .

 Here We Present Evidence that Checkpoint Inhibition May Not be The Primary Mechanism of Action for Efficacy of Anti-CTLA-4 Antibodies .

Instead, a Primary mechanism For Efficacy is FcR-mediated Treg Depletion in the Tumor MicroEnvironment .

We identified a Monoclonal Antibody (mAb), GIGA-564, that binds to CTLA-4 at an epitope that differs from IPILIMUMAB’s by only a few amino acids, yet has limited Checkpoint Inhibitor Activity .

SURPRISINGLY, GIGA-564 HAS SUPERIOR ANTI-TUMOR ACTIVITY COMPARED TO IPILIMUMAB IN A MURINE MODEL .

 GIGA-564 Also Induces less Treg Proliferation and has Increased Ability to Inducein VitroFcR Signaling Andin VivoDepletion of Intratumoral Tregs .

Further experiments Showed that the Enhanced FcR Activity of GIGA-564 likely contributes to its Enhanced ANTI-TUMOR Activity .

Importantly, We Also Showed That GIGA-564 Was Associated With Lower Toxicity in Murine Models .

 Our Work Suggests That New Anti-CTLA-4 Drugs Should be Optimized For Treg Depresión Rather Than Checkpoint Inhibition .

Erica Stone,Vice President, Oncology,GigaGen Inc .

Last Published : 13/Jan/23 .