EHA 2019 – Expert commentary – Gene therapy and cellular therapy: the present is bright, the future may be sparkling

  • Elena Riboldi — Agenzia Zoe
  • Univadis
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Franco Locatelli is a Full Professor of Paediatrics at the University of Pavia and Head of the Department of Paediatric Haematology and Oncology, IRCCS Ospedale Bambino Gesù, Rome (Italy). He has provided relevant contributions in the field of hematological disorders of childhood. His current research focus on CAR-T cells and gene therapy for thalassemia.


  • Several presentations at the EHA Congress have focused on gene and cellular therapy for both treating inherited disorders and for treating cancer.
  • Regarding inherited disorders, there are two main settings where data are particularly promising: one is gene therapy for β-thalassaemia and the other one is gene therapy for sickle cell disease.
  • About CAR-T cell therapy, there were both company-driven study updates and also some data from academic institutions confirming that B-cell precursor acute lymphoblastic leukaemia benefits from the treatment with second generation CD19-directed CAR-T cells.
  • Results in adults with aggressive B cell non-Hodgkin lymphomas, in particular diffuse large B cell lymphoma and follicular lymphoma, demonstrate that these patients can be successfully treated with the CAR-T cell approach.
  • The academic studies prove that academic institutions can offer the possibility to treat patients outside trials driven and conducted under the supervision of companies: this is an opportunity for enlarging the number of patients that can be treated.
  • There are also very exciting data on patients with multiple myeloma; in the future we can expect that other hematological malignancies, including chronic lymphocytic leukaemia or maybe also CD30-positive lymphomas, could be successfully treated with CAR-T cells.
  • There is also a great enthusiasm for translating the CAR-T cell approach in solid tumours.
  • In our hospital we are running a trial in children with neuroblastoma: despite the fact that we were treating relapsed/refractory very advanced disease, we obtained promising results in term of response, this suggesting that when the therapy will be used in an earlier phase of the disease results will be better.
  • These advanced therapy medical products must be tightly controlled, monitored, and preliminarily approved by the regulatory agencies before being employed in human beings.
  • At the moment we cannot offer these therapies to newly diagnosed patients, therefore the careful selection of the patients is a key point.
  • The cost of these therapies is really an issue to be addressed, especially in those countries where there is a national health system.
  • We are working on trials using CAR-natural killer (NK) cells, because this strategy could offer several advantages in comparison to CAR-T cells.
  • First, NK cell-related toxicity could possibly be lower in comparison to that of CAR-T cells because the cytokines production of NK cells has a less toxic, more favourable profile.
  • Second, these cells could be immediately available: we can figure out to prepare banks of CAR-NK cells.
  • This could overcome two problems: the time needed to prepare CAR-T cells and the obstacle represented by the fact that a proportion of patients cannot benefit from the CAR-T cells because it is impossible to generate the product.
  • In fact, some patients in advanced state of disease either do not have enough T cells or have a very poor T cell function, precluding the generation of a good CAR-T cell product.
  • Last, the cytotoxic effect of NK cells is higher than that of T cells: in other words, NK cells are the most potent cytotoxic lymphocytes that we have in our body.