Pre-clinical validation of a pan-cancer CAR-T cell immunotherapy targeting nfP2X7.
Veronika BandaraJade FoengBatjargal GundsambuuTodd S NortonSilvana NapoliDylan J McPeakeTimona S TyllisElaheh Rohani-RadCaitlin AbbottStuart J MillsLih Y TanEmma J ThompsonVasiliki M WilletVictoria J NikitarasJieren ZhengIain ComerfordAdam JohnsonJustin CoombsMartin K OehlerCarmela RicciardelliAllison J CowinClaudine S BonderMichael C JensenTimothy J SadlonShaun R McCollSimon C BarryPublished in: Nature communications (2023)
Chimeric antigen receptor (CAR)-T cell immunotherapy is a novel treatment that genetically modifies the patients' own T cells to target and kill malignant cells. However, identification of tumour-specific antigens expressed on multiple solid cancer types, remains a major challenge. P2X purinoceptor 7 (P2X7) is a cell surface expressed ATP gated cation channel, and a dysfunctional version of P2X7, named nfP2X7, has been identified on cancer cells from multiple tissues, while being undetectable on healthy cells. We present a prototype -human CAR-T construct targeting nfP2X7 showing potential antigen-specific cytotoxicity against twelve solid cancer types (breast, prostate, lung, colorectal, brain and skin). In xenograft mouse models of breast and prostate cancer, CAR-T cells targeting nfP2X7 exhibit robust anti-tumour efficacy. These data indicate that nfP2X7 is a suitable immunotherapy target because of its broad expression on human tumours. CAR-T cells targeting nfP2X7 have potential as a wide-spectrum cancer immunotherapy for solid tumours in humans.
Keyphrases
- prostate cancer
- papillary thyroid
- squamous cell
- induced apoptosis
- endothelial cells
- end stage renal disease
- poor prognosis
- cell cycle arrest
- cell surface
- mouse model
- lymph node metastasis
- signaling pathway
- immune response
- stem cells
- chronic kidney disease
- single cell
- radical prostatectomy
- childhood cancer
- multiple sclerosis
- endoplasmic reticulum stress
- oxidative stress
- brain injury
- induced pluripotent stem cells
- cell proliferation
- functional connectivity
- climate change
- resting state
- human health
- mesenchymal stem cells
- patient reported outcomes
- young adults
- soft tissue
- blood brain barrier
- cerebral ischemia