Abstract 2451: A novel humanized anti-CD40 RabMAb exhibits potent efficacy in preclinical models

Monoclonal antibodies directed against B cell antigens have shown clinical benefits to hematologic malignancies. CD40 is a member of the TNFR superfamily and is a target for potential treatment of B cell lineage hematological malignancies as well as certain carcinomas. To date, majority of the therapeutic monoclonal antibodies are of murine origin. To evaluate the therapeutic potential of rabbit monoclonal antibodies (RabMAb®), we generated functional RabMAbs against CD40 using Epitomics' RabMAb® platform. Here we report the characterization of EPI0050, a novel humanized anti-CD40 rabbit monoclonal antibody. EPI0050 specifically recognizes the CD40 ligand binding domain and selectively blocks the ligand binding to CD40. EPI0050 itself exhibits modest agonist effects as shown in the up-regulation of CD80, CD83 and CD86 in differentiated dendritic cells and direct inhibition of CD40 positive malignant B cells. EPI0050 bound CD40 strongly without much internalization, which conferred to a potent ADCC effect in vitro. In an established preclinical Ramos lymphoma model, EPI0050 significantly inhibited tumor growth with a long-term stabilization of the tumor post dosing as compared with Rituximab and another anti-CD40 antibody. EPI0050 was also able to regress established rebound tumors post Rituximab treatment. More animal models and MOA are being explored for EPI0050. Both in vitro and in vivo results support the preclinical and clinical development of EPI0050 as a bio-better tumor therapy. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2451.