Oral Presentation Eradicate Cancer 2018

Validation of a novel CAR-T cell targeting non functional P2X7 (#27)

Veronika Bandara 1 , Timothy Sadlon 2 , Justin Coombs 3 , Michael Jensen 4 , Simon C Barry 2
  1. Robinson Research Institute, North Adelaide, SA, Australia
  2. RRI/WCHN, North Adelaide, SA, Australia
  3. Carina Biotechnology, Adelaide, SA, Australia
  4. Ben Towne Centre for Childhood Cancer Research , Seattle Children's Research Institute, Seattle, WA, USA

One of the most significant hurdles to the wide scale delivery of cancer immunotherapies is the need for novel  broad cancer specific targets. We have developed a novel CAR-T cell against the  extracellular domain of a non functional form of the ATP transporter P2X7, (nfP2x7) which is  expressed on  multiple cancer cells, but not normal cells.  P2X7 is widely expressed on  many cell types and is an active ATP transporter linked to cell survival, however, the non functional form of P2X7 is conformationally altered, which reveals an epitope not present on the WT P2X7 receptor.  We have generated a set of binders to this epitope and assembled them into a chimeric antigen receptor. Using lentiviral gene delivery we have expressed this novel CAR-T on human CD8 cells and performed specificity screening and functional assay  of cytotoxicity. We have pilot data suggesting this CAR-T cell can directly target breast cancer cells in vitro, and only the nfP2X7 epitope is recognised by the CAR-T. We have validated these findings with killing assays on a number of other cancer cell lines, suggesting that nfP2x7 is a valid target on a number of cancer types.  We now aim to demonstrate broad anti cancer specificity using tissue arrays and in vivo tumour killing assays as part of pre-clinical validation.