Targeting EBV positive cancers with affinity enhanced T cell receptors — ASN Events
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  3. Targeting EBV positive cancers with affinity enhanced T cell receptors

Targeting EBV positive cancers with affinity enhanced T cell receptors (#408)

Yide Wong 1 , Emma Gostick 2 , Martine Lomax 3 , Annelise Vuidepot 3 , Emma Baston 3 , William Shingler 3 , Namir Hassan 3 , Joseph Dukes 3 , Corey Smith 4 , Rajiv Khanna 4 , Kristin Ladell 2 , David K Cole 2 , Andrew K Sewell 2 , Scott R Burrows 4 , Bent Jakobsen 3 , David A Price 2 , John J Miles 1
  1. James Cook University, Smithfield, QLD, Australia
  2. Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
  3. Immunocore Limited, Milton Park, Oxon, United Kingdom
  4. QIMR Berghofer, Herston, QLD, Australia

Epstein-Barr virus (EBV) is associated with over 30 different diseases and malignancies. The pathogen is associated with over 300,000 cases of cancer annually and is thought to be involved in various pathologies affecting over one million people annually. Currently, no commercially available EBV specific therapy or vaccine exists. Using phage display directed evolution; we generated a panel of affinity enhanced T cell receptors (TCR) that targeted an EBV antigen from LMP2. We then generated Immune Mobilising Monoclonal TCRs Against Cancer (ImmTACs) by fusing an anti-CD3 effector payload to the constant region of the TCR. In soluble form, EBV ImmTACs were able to redirect T cell specificity in vitro in low picomolar concentrations against nasopharyngeal carcinoma, Burkitt's lymphoma, gastric carcinoma, diffuse large B-cell lymphoma and lymphoblastic cell lines. Using multiparametric flow cytometry, we observed EBV ImmTACs could redirect large numbers of polyfunctional CD8+ and CD4+ T cells against EBV positive cancers. We are currently testing these soluble therapeutics in humanised and tumor xenograft EBV mouse models to gauge safety and in vivoefficacy and we have began to observe signs of its potency in our animal studies. EBV ImmTACs are first in class and represent a promising new “off-the-shelf” therapy against EBV associated cancers and could be a significant stride forward in treating the wide spectrum of diseases associated with this pathogen.

  1. Liddy, N., et al. (2012). "Monoclonal TCR-redirected tumor cell killing." Nat Med 18(6): 980-987.
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