title: Acute Myeloid Leukemia Targeting by Chimeric Antigen Receptor T Cells: Bridging the Gap from Preclinical Modeling to Human Studies.
abstract: Acute myeloid leukemia (AML) still represents an unmet clinical need for adult and pediatric high-risk patients, thus demanding advanced and personalized therapies. In this regard, different targeted immunotherapeutic approaches are available, ranging from naked monoclonal antibodies (mAb) to conjugated and multifunctional mAbs (i.e., BiTEs and DARTs). Recently, researchers have focused their attention on novel techniques of genetic manipulation specifically to redirect cytotoxic T cells endowed with chimeric antigen receptors (CARs) toward selected tumor associated antigens. So far, CAR T cells targeting the CD19 antigen expressed by B-cell origin hematological cancers have gained impressive clinical results, leading to the possibility of translating the CAR platform to treat other hematological malignancies such as AML. However, one of the main concerns in the field of AML CAR immunotherapy is the identification of an ideal target cell surface antigen, being highly expressed on tumor cells but minimally present on healthy tissues, together with the design of an anti-AML CAR appropriately balancing efficacy and safety profiles. The current review focuses mainly on AML target antigens and the related immunotherapeutic approaches developed so far, deeply dissecting methods of CAR T cell safety improvements, when designing novel CARs approaching human studies.
authors.affiliation: 1 Molecular Therapy Unit, Tettamanti Research Center, Pediatric Clinic, University of Milano Bicocca , San Gerardo Hospital/MBBM Foundation, Monza, Italy.
authors.forename: Maria Caterina
authors.initials: MC
authors.lastname: Rotiroti
authors.affiliation: 1 Molecular Therapy Unit, Tettamanti Research Center, Pediatric Clinic, University of Milano Bicocca , San Gerardo Hospital/MBBM Foundation, Monza, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Arcangeli
authors.affiliation: 2 Innovative Immunotherapies Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Hospital Scientific Institute, Vita-Salute San Raffaele University , Milan, Italy .
authors.forename: Monica
authors.initials: M
authors.lastname: Casucci
authors.affiliation: 1 Molecular Therapy Unit, Tettamanti Research Center, Pediatric Clinic, University of Milano Bicocca , San Gerardo Hospital/MBBM Foundation, Monza, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Perriello
authors.affiliation: 2 Innovative Immunotherapies Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Hospital Scientific Institute, Vita-Salute San Raffaele University , Milan, Italy .
authors.forename: Attilio
authors.initials: A
authors.lastname: Bondanza
authors.affiliation: 1 Molecular Therapy Unit, Tettamanti Research Center, Pediatric Clinic, University of Milano Bicocca , San Gerardo Hospital/MBBM Foundation, Monza, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.affiliation: 1 Molecular Therapy Unit, Tettamanti Research Center, Pediatric Clinic, University of Milano Bicocca , San Gerardo Hospital/MBBM Foundation, Monza, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Tettamanti
authors.affiliation: 1 Molecular Therapy Unit, Tettamanti Research Center, Pediatric Clinic, University of Milano Bicocca , San Gerardo Hospital/MBBM Foundation, Monza, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Biagi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell
keywords: AML; CAR-T cells; immunotherapy; preclinical models; targeted therapies