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Vol. 42. Issue S1.
Pages 7 (October 2020)
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Vol. 42. Issue S1.
Pages 7 (October 2020)
SP 12
Open Access
CAR T-cell in children all
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Francesco Saglio1,2
1 Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Torino, Italy
2 University of Turin, Turin, Italy
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Chimeric Antigen Receptor (CAR)-T cell therapy is emerging as one of the most powerful and promising therapeutictool for the treatment of malignat diseases. CAR-T cells are T-lymphocytes modified in vitro to harbor an artificial molecular construct (CAR) made by an extracellular domain consisting of a single-chain variable fragment (scFv) recognizing a specific tumor antigen joined to a transmembrane domain which is linked to the signaling unit CD3ζ and co-stimulatory units CD28 or 4-1BB of the T-cell receptor, making them capable to recognize and to kill tumor's cell in a HLA-independent manner.CAR T-cell therapy consists in the selection of patient's normal T-cells via leukapheresis, activation, transduction to express CARs using lentiviral or retroviral vectors, expansion of transduced cells and infusion of the final product back to the patient. After the CAR T-cells are infused back into the patient, the engineered cells proliferate, recognize and kill tumor cells bearing the specific antigen the CAR is directed against. Most of the current clinical trials have been with anti-CD19 CAR T-cells directed against the antigen CD19, mainly expressed by Acute Lymphoblastic Leukemia and B-cells Non Hodgkin Lymphomas.

In recent years US Food and Drug Administration (FDA) and European Medicine Agency (EMA) approved CD19 CAR T-cells in patients affected by relapsed and refractory ALL under the age of 25 years and this technology is moving from an experimental approach available for very selected patients treated in a small number of Centers to a standard-of-care therapy available almost worldwide.

The diffusion of this technology requires a re-definition of the role of all the other therapy options currently available including other forms of immuno-therapy as monoclonal antibodies, bi-specific monoclonal antibodies and, upon all, allogeneic hematopoietic stem cell transplantation (alloHSCT).

Until now data are limited, and the above-mentioned question is far from being answered but there are some observations derived from pivotal clinical trials that probably will help us in building future trials aimed to define this topic.

Another open question is represented by the persistence of these cells in the patients that is related to the definition of the need for patients responding to CAR-T cells to proceed to other therapies, especially to alloHSCT, to consolidate disease remission. Moreover CAR-T cells are characterized by some peculiar side effects as the Cytokines Release Syndrome or CNS toxicity that if are not properly detected and treated may lead to very severe consequences with a significant mortality rate.

Finally, some technological, practical and economical considerations need to be defined in order to extend the use of this technology worldwide, in respect to the other currently available therapies.

Idiomas
Hematology, Transfusion and Cell Therapy
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