Honors & Awards


  • Postdoctoral Fellowship, American Italian Cancer Foundation (AICF) (2020-2021)
  • Beat Leukemia Fellowship, Societa' Italiana di Ematologia Sperimentale (SIES) (2018 –2019)
  • PhD Fellowship, Translational and Molecular Medicine program, University of Milano-Bicocca, Italy (2015-2018)
  • Post-graduate Fellowship, “M. Tettamanti” Research Center, Monza, Italy (2015)

Professional Education


  • PhD, University of Milano-Bicocca Milano, Italy, Translational and Molecular Medicine (2019)
  • MS, University of Milano-Bicocca Milano, Italy, Medical Biotechnology (2015)
  • BS, Magna Graecia University, Catanzaro, Italy, Biotechnology (2012)

Stanford Advisors


All Publications


  • Targeting CD33 in Chemoresistant AML Patient-Derived Xenografts by CAR-CIK Cells Modified with an Improved SB Transposon System MOLECULAR THERAPY Rotiroti, M., Buracchi, C., Arcangeli, S., Galimberti, S., Valsecchi, M., Perriello, V., Rasko, T., Alberti, G., Magnani, C., Cappuzzello, C., Lundberg, F., Pande, A., Dastoli, G., Introna, M., Serafini, M., Biagi, E., Izsvak, Z., Biondi, A., Tettamanti, S. 2020; 28 (9): 1974–86

    Abstract

    The successful implementation of chimeric antigen receptor (CAR)-T cell therapy in the clinical context of B cell malignancies has paved the way for further development in the more critical setting of acute myeloid leukemia (AML). Among the potentially targetable AML antigens, CD33 is insofar one of the main validated molecules. Here, we describe the feasibility of engineering cytokine-induced killer (CIK) cells with a CD33.CAR by using the latest optimized version of the non-viral Sleeping Beauty (SB) transposon system "SB100X-pT4." This offers the advantage of improving CAR expression on CIK cells, while reducing the amount of DNA transposase as compared to the previously employed "SB11-pT" version. SB-modified CD33.CAR-CIK cells exhibited significant antileukemic activity in vitro and in vivo in patient-derived AML xenograft models, reducing AML development when administered as an "early treatment" and delaying AML progression in mice with established disease. Notably, by exploiting an already optimized xenograft chemotherapy model that mimics human induction therapy in mice, we demonstrated for the first time that CD33.CAR-CIK cells are also effective toward chemotherapy resistant/residual AML cells, further supporting its future clinical development and implementation within the current standard regimens.

    View details for DOI 10.1016/j.ymthe.2020.05.021

    View details for Web of Science ID 000571942900005

    View details for PubMedID 32526203

    View details for PubMedCentralID PMC7474266

  • Balance of Anti-CD123 Chimeric Antigen Receptor Binding Affinity and Density for the Targeting of Acute Myeloid Leukemia MOLECULAR THERAPY Arcangeli, S., Rotiroti, M., Bardelli, M., Simonelli, L., Magnani, C., Biondi, A., Biagi, E., Tettamanti, S., Varani, L. 2017; 25 (8): 1933–45

    Abstract

    Chimeric antigen receptor (CAR)-redirected T lymphocytes are a promising immunotherapeutic approach and object of pre-clinical evaluation for the treatment of acute myeloid leukemia (AML). We developed a CAR against CD123, overexpressed on AML blasts and leukemic stem cells. However, potential recognition of low CD123-positive healthy tissues, through the on-target, off-tumor effect, limits safe clinical employment of CAR-redirected T cells. Therefore, we evaluated the effect of context-dependent variables capable of modulating CAR T cell functional profiles, such as CAR binding affinity, CAR expression, and target antigen density. Computational structural biology tools allowed for the design of rational mutations in the anti-CD123 CAR antigen binding domain that altered CAR expression and CAR binding affinity without affecting the overall CAR design. We defined both lytic and activation antigen thresholds, with early cytotoxic activity unaffected by either CAR expression or CAR affinity tuning but later effector functions impaired by low CAR expression. Moreover, the anti-CD123 CAR safety profile was confirmed by lowering CAR binding affinity, corroborating CD123 is a good therapeutic target antigen. Overall, full dissection of these variables offers suitable anti-CD123 CAR design optimization for the treatment of AML.

    View details for DOI 10.1016/j.ymthe.2017.04.017

    View details for Web of Science ID 000406989700022

    View details for PubMedID 28479045

    View details for PubMedCentralID PMC5542631

  • Acute Myeloid Leukemia Targeting by Chimeric Antigen Receptor T Cells: Bridging the Gap from Preclinical Modeling to Human Studies HUMAN GENE THERAPY Rotiroti, M., Arcangeli, S., Casucci, M., Perriello, V., Bondanza, A., Biondi, A., Tettamanti, S., Biagi, E. 2017; 28 (3): 231–41

    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.

    View details for DOI 10.1089/hum.2016.092

    View details for Web of Science ID 000397570400003

    View details for PubMedID 27967241