Invited Speakers Eradicate Cancer 2018

Using cell banks to treat opportunistic infection and haematological malignancy (#31)

David Gottlieb 1
  1. University of Sydney, Westmead Hospital, Wentworth, NSW, Australia

Infusion of HLA matched antigen specific T-cells targeting viruses such as Epstein-Barr virus and cytomegalovirus is an effective therapy to prevent and treat opportunistic infections in immunocompromised individuals. In the setting of stem cell transplantation, cell products are most frequently derived from the HLA matched stem cell donor and are prepared in advance of the infection in order to avoid a prolonged delay between diagnosis and treatment. Inevitably, this approach results in some products never being administered, since many patients fail to develop the specific infection for which the T-cell therapy has been generated. To avoid the human, reagent and storage costs associated with product wastage, the safety and efficacy of infusing cryopreserved antigen specific T-cells from partially HLA matched unrelated donors has been investigated. The need for only partially HLA matching reduces the number of products required for a bank to provide wide patient coverage if donors with common HLA alleles are chosen for cell generation. We have investigated the use of 3rd party partially HLA matched virus-specific T-cells for refractory CMV, EBV and adenovirus infections after allogeneic stem cell transplant and demonstrated both short and long term efficacy. We are currently evaluating the same strategy in allogeneic transplant recipients at the first evidence of viral reactivation. Products consisting of T-cells responding to fungal antigens can also be created. Fungus-specific T-cells are mostly CD4+ and release cytokines including tumour necrosis factor alpha and interferon gamma in response to antigen stimulation. Specific cytokine secretion and proliferation responses are mediated via HLA-DR. We propose to establish a trial of 3rd party HLA-DR matched fungus-specific T-cells for allogeneic stem cell transplant recipients with invasive fungal disease. Finally, infusion of T-cells recognising tissue or cancer antigens from cryopreserved banks is a practical option for cancer immunotherapy. We created a “virtual” bank of cell products from donated haemopoietic progenitor cells or donor lymphocytes that were due for discard from participating laboratories. We treated 4 elderly AML patients with chemotherapy followed by 2-3 infusions of partially HLA matched products from unrelated donors. Infusions were associated with fever, infection and rash but no patient developed graft versus host disease. 2 patients relapsed but 2 remain alive up to 432 days after treatment. Donor cell persistence was observed up to 60 days post infusion. Cryopreserved banks of antigen specific T-cells targeting infectious, tissue and cancer antigens may facilitate the application of cell therapy in infections and cancer.