Killer T cell Therapy for Nasopharyngeal Carcinoma

Epstein-Barr virus (EBV) is associated with a number of human malignancies including nasopharyngeal carcinoma (NPC). 100% of undifferentiated NPC tumours are EBV- positive meaning the virus is localised to the tumour cells. We are attempting to develop immunotherapy as an alternate treatment for nasopharyngeal carcinoma (NPC) in addition to radiotherapy, chemotherapy and surgery. This immunotherapy would be in the form of adoptive transfer. This requires that a certain type of white blood cell found in the body known as “killer T-cells” or technically "cytotoxic T lymphocytes" (CTL) be isolated from the NPC patient’s own blood. These T cells are trained in the laboratory to become more efficient at recognising and destroying EBV infected tumour cells. Adoptive transfer is when the EBV-specific T cells are given back to the patient via intravenous infusions. This phase I adoptive immunotherapy trial aims to determine the safety, tolerability and efficacy of adoptive transfer of EBV specific T cells for NPC. The study will be carried out in collaboration with The University of Hong Kong, The Queensland Institute of Medical Research (QIMR) and The Princess Alexandra Hospital, Brisbane. A total of 50 eligible participants will be enrolled on the trial (35 from Hong Kong and 15 from the Princess Alexandra Hospital). Following informed consent, a 200-400ml blood sample will be collected from each participant and transported to the Q-Gen laboratory at QIMR in Brisbane where laboratory staff will begin to grow the T cells with a recombinant adenovirus. This process will take about 15 days. The recombinant adenovirus expresses small fragments from NPC-associated viral proteins this technique is used to stimulate the killer T cells in the laboratory. This adenovirus has been modified in such a way that it is non-infectious and does not cause any disease. This stimulation should result in the T cells being able to recognize EBV proteins on the NPC tumour that are there because of the EBV in the tumour. After recognising these proteins, the T cells will try to kill the tumour. After the killer T cells have been grown they will be purified and all residual adenovirus removed. They will be tested for safety, sterility and specific activity before being transported back to the treating hospital. The participants will undergo several baseline assessments, including blood tests. The killer T cells will be given back to the participant via adoptive transfer. Infusions of between 20-40 x 10^6 CTL will be given intravenously on a fortnightly basis, for up to six infusions. Participants will be monitored once a fortnight for the first 12 weeks and then once a month for four months. Monitoring will involve a series of blood tests and MRI scans. Participants will be on the trial for a total of 33 weeks.