Abstract 2900: IMCgp100: A novel bi-specific biologic for the treatment of malignant melanoma
Authors: Hassan Namir J. , Bossi Giovanna , Baker Debbie , Adams Katherine , Harper Jane , Dukes Joseph , Liddy Nathaniel , Paston Samantha , McGrath Yvonne , Mahon Tara , Molloy Peter , Sami Malkit , Baston Emma , Cameron Brian , Johnson Andrew , Vuidepot Annelise , Linette Gerry , Kalos Michael , June Carl , Jakobsen Bent 
Published: May 2015

Abstract
Despite significant advances in the treatment of metastatic melanoma, long-term remission for the majority of patients remains elusive. Kinase inhibitors provide potent but short-term responses for a significant proportion of patients and immunotherapy elicits long-term responses with the prospect of cure, but only in a minority.
IMCgp100 is a novel bi-specific immunotherapy comprising a soluble, affinity enhanced, T cell receptor (TCR) specific for the melanoma-associated antigen gp100, fused to an anti-CD3 specific antibody fragment (scFv). The engineered TCR portion of the drug targets and binds the gp100 peptide 280-288 antigen, which is over-expressed and presented by HLA-A2 on the surface of melanoma cells. The anti-CD3 scFv portion captures and redirects T cells to kill the melanoma cells, while normal antigen negative tissues are unaffected. Here, we present data which provides the foundation for the clinical observations. In vitro, IMCgp100 is demonstrated to potently redirect T cells from late stage cancer patients to target melanoma tumors exhibiting HLA-down regulation, even in the presence of high numbers of regulatory T cells. Target cell killing is observed within hours and is specific for gp100. In addition killing is associated with the release of various pro-inflammatory cytokines and chemokines as well as cross-presentation of gp100 and other melanoma-associated antigens by dendritic cells. Thus, IMCgp100 demonstrates the potential to elicit potent short-term responses and trigger longer-term anti melanoma activity in vivo.
IMCgp100 is undergoing Phase I clinical testing in patients with advanced malignant melanoma; with the maximum tolerated dose having been established. The drug is well tolerated with evidence of tumor shrinkage. Analyses of serum samples obtained from patients on the trial demonstrate T cell mobilisation and transient drug mediated increases in various cytokines and chemokines, some of which are reported to play a key role in anti-melanoma responses. These data support the potential of IMCgp100 as an effective treatment for malignant melanoma.
Citation Format: Namir J. Hassan, Giovanna Bossi, Debbie Baker, Katherine Adams, Jane Harper, Joseph Dukes, Nathaniel Liddy, Samantha Paston, Yvonne McGrath, Tara Mahon, Peter Molloy, Malkit Sami, Emma Baston, Brian Cameron, Andrew Johnson, Annelise Vuidepot, Gerry Linette, Michael Kalos, Carl June, Bent Jakobsen. IMCgp100: A novel bi-specific biologic for the treatment of malignant melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2900. doi:10.1158/1538-7445.AM2014-2900