IMCgp100: a novel bi-specific biologic for the treatment of malignant melanoma
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1
Immunocore Ltd, United Kingdom
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; normal antigen negative tissues are spared destruction. In vitro, IMCgp100 potently redirects T cells from late stage cancer patients to target melanoma tumours exhibiting HLA-down regulation even in the presence of high numbers of regulatory T cells. Target cell killing is observed within hours, and, is associated with the release of pro-inflammatory cytokines and dendritic cell cross-presentation of gp100 and other melanoma-associated antigens. 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 advanced melanoma patients; 22 patients have received single IV infusions so far and 7 patients have subsequently received weekly infusions for 6 weeks. The drug is well tolerated with evidence of T cell mobilisation, specific cytokine release and tumour shrinkage after dosing.
Keywords:
ImmTAC,
Immunotherapy,
gp100 Melanoma Antigen,
oncology,
malignant melanoma
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
Hassan
NJ
(2013). IMCgp100: a novel bi-specific biologic for the treatment of malignant melanoma.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00676
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Received:
12 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Namir J Hassan, Immunocore Ltd, Abingdon, United Kingdom, namir.hassan@immunocore.com