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Journal of autoimmunity v.85, 2017년, pp.141 - 152   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Redirecting T cells with Chimeric Antigen Receptor (CAR) for the treatment of childhood acute lymphoblastic leukemia

Biondi, Andrea    (Corresponding author.  ); Magnani, Chiara F.   Tettamanti, Sarah   Gaipa, Giuseppe   Biagi, Ettore  
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    Abstract Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Nowadays the survival rate is around 85%. Nevertheless, an urgent clinical need is still represented by primary refractory and relapsed patients who do not significantly benefit from standard approaches, including chemo-radiotherapy and hematopoietic stem cell transplantation (HSCT). For this reason, immunotherapy has so far represented a challenging novel treatment opportunity, including, as the most validated therapeutic options, cancer vaccines, donor-lymphocyte infusions and tumor-specific immune effector cells. More recently, unexpected positive clinical results in ALL have been achieved by application of gene-engineered chimeric antigen expressing (CAR) T cells. Several CAR designs across different trials have generated similar response rates, with Complete Response (CR) of 60–90% at 1 month and an Event-Free Survival (EFS) of 70% at 6 months. Relevant challenges anyway remain to be addressed, such as amelioration of technical, cost and feasibility aspects of cell and gene manipulation and the necessity to face the occurrence of relapse mechanisms. This review describes the state of the art of ALL immunotherapies, the novelties in terms of gene manipulation approaches and the problems emerged from early clinical studies. We describe and discuss the process of clinical translation, including the design of a cell manufacturing protocol, vector production and regulatory issues. Multiple antigen targeting and combination of CAR T cells with molecular targeted drugs have also been evaluated as latest strategies to prevail over immune-evasion. Highlights Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Nowadays relapsed ALL has a survival rate (CAR) T cells, reaching a Complete Response (CR) of 60–90% at 1 month and an Event-Free Survival (EFS) of 70% at 6 months. Ameliorations are in development in the CAR-T cell approach, as the use of transposons as a non-viral gene-transfer method. Tumor escape represents the major drawback. Dual targeting and immunomodulation constitute promising perspectives.


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