Andrea Biondi
e-mail: andrea.biondi AT unimib.it
affiliation: Università di Milano Bicocca
research area(s): Experimental Medicine, Stem Cells And Regenerative Medicine
Course:
Basic and Applied Immunology
University/Istitution: Università Vita-Salute San Raffaele
University/Istitution: Università Vita-Salute San Raffaele
Education
1979 M.D. at the University of Milan, School of Medicine, maximum cum laude.
1982 Specialist in Pediatrics, University of Milan
1994 Specialist in Hematology, University of Bari
Research fellowships
1979/1982 Research fellow in the Laboratory of Human Immunology "M.Negri" Institute, Milan, Italy
1982/1984 "Research Associate in Pathology" - Department of Tumor Immunology, Dana Farber Cancer Institute, Harvard Medical School, Boston, USA
1984/1986 Research Associate in the Laboratory of Human Immunology "M.Negri" Institute, Milan, Italy
1986/1987 "Research Associate in Medicine" - Department of Bioresearch, The Ontario Cancer Institute, Toronto, Canada
Professional position
1987/1998 Physician staff, Pediatric Dept, University of Milan, H.S.Gerardo Monza (MI) Italy
1998/1999 Assistant Professor of Pediatrics, University of Milano, Milan, Italy
1999/2000 Assistant Professor of Pediatrics, University of Milano-Bicocca, Milan, Italy
2000/2006 Associate Professor of Pediatrics, University of Milano-Bicocca, Milan, Italy
2004/2008 Director, School of Oncology, University of Milano-Bicocca, Milan, Italy
2006/2008 Coordinator, Master 1st Level in Palliative Cares, University of Milano-Bicocca, Milan, Italy
Since 1994 Head,"M.Tettamanti" Research Center for leukemic and hematological diseases of children, H.S. Gerardo, Monza (MI) Italy
Since 2003 Head, "S. Verri" Cellular and Gene Therapy Laboratory, H. S. Gerardo, Monza (MI) Italy
Since 2006 Full professor of Pediatrics, University of Milano-Bicocca, Milan, Italy
Since 2006 Scientific Director, Fondazione M. Tettamanti M. De Marchi Onlus, Monza (MI), Italy
Since 2006 President, Consorzio Genetica Molecolare Umana, Monza (MI), Italy
Since 2007 Coordinator, Ph.D. Program in Translational and Molecular Medicine " University of Milano-Bicocca, Milan, Italy (www.dimet.org)
Since 2008 Coordinator, Master 1st Level in Pediatric Nursing, University of Milano-Bicocca, Milan, Italy
Since 2008 Director, School of Pediatrics, University of Milano-Bicocca, Milan, Italy
11/01/2009 Director, Department of Paediatrics, University of Milano-Bicocca, San Gerardo Hospital, Monza (MI), Italy
11/17/2009 President, School PhD Ph.D. Program in Translational and Molecular Medicine " University of Milano-Bicocca, Milan, Italy (www.dimet.org)
Societies
2004-2008 President SIOP Europe
Since 1985 Member of the Italian Group of Cooperation in Immunology
Since 1991 Member of the Italian Society of Experimental Hematology
Since 1992 Member of the American Society of Hematology
Since 1992 Member of the Italian Society of Pediatric Hematology and Oncology (AIEOP)
Since 1997 Member of the International Society of Pediatric Oncology (SIOP)
Since 2003 Member of the EHA Scientific Program Committee
Scientific Journals
- Editorial Board of Pediatric Blood & Cancer and The European Journal of Cancer
- Reviewer of Annals of Oncology, Blood, British Journal of Haematology, European Journal of Cancer, European Journal of Haematology, Genes Chromosomes and Cancer, The Hematology Journal/Haematologica, International Journal of Cancer, Leukemia.
Reviewer for funding programs and site visits of international organisations/agencies
- Cancer Research UK
- Children Oncology Group, USA
- Leukemia Research Fund, UK
- National Cancer Institute/National Institute of Health, USA
- OncoSuisse. Swiss Federation Against Cancer, CH
- Stichting Kindergeneeskunde Kankeronderzoek (SKK), NL
- International Union Against Cancer (UICC), CH
1979 M.D. at the University of Milan, School of Medicine, maximum cum laude.
1982 Specialist in Pediatrics, University of Milan
1994 Specialist in Hematology, University of Bari
Research fellowships
1979/1982 Research fellow in the Laboratory of Human Immunology "M.Negri" Institute, Milan, Italy
1982/1984 "Research Associate in Pathology" - Department of Tumor Immunology, Dana Farber Cancer Institute, Harvard Medical School, Boston, USA
1984/1986 Research Associate in the Laboratory of Human Immunology "M.Negri" Institute, Milan, Italy
1986/1987 "Research Associate in Medicine" - Department of Bioresearch, The Ontario Cancer Institute, Toronto, Canada
Professional position
1987/1998 Physician staff, Pediatric Dept, University of Milan, H.S.Gerardo Monza (MI) Italy
1998/1999 Assistant Professor of Pediatrics, University of Milano, Milan, Italy
1999/2000 Assistant Professor of Pediatrics, University of Milano-Bicocca, Milan, Italy
2000/2006 Associate Professor of Pediatrics, University of Milano-Bicocca, Milan, Italy
2004/2008 Director, School of Oncology, University of Milano-Bicocca, Milan, Italy
2006/2008 Coordinator, Master 1st Level in Palliative Cares, University of Milano-Bicocca, Milan, Italy
Since 1994 Head,"M.Tettamanti" Research Center for leukemic and hematological diseases of children, H.S. Gerardo, Monza (MI) Italy
Since 2003 Head, "S. Verri" Cellular and Gene Therapy Laboratory, H. S. Gerardo, Monza (MI) Italy
Since 2006 Full professor of Pediatrics, University of Milano-Bicocca, Milan, Italy
Since 2006 Scientific Director, Fondazione M. Tettamanti M. De Marchi Onlus, Monza (MI), Italy
Since 2006 President, Consorzio Genetica Molecolare Umana, Monza (MI), Italy
Since 2007 Coordinator, Ph.D. Program in Translational and Molecular Medicine " University of Milano-Bicocca, Milan, Italy (www.dimet.org)
Since 2008 Coordinator, Master 1st Level in Pediatric Nursing, University of Milano-Bicocca, Milan, Italy
Since 2008 Director, School of Pediatrics, University of Milano-Bicocca, Milan, Italy
11/01/2009 Director, Department of Paediatrics, University of Milano-Bicocca, San Gerardo Hospital, Monza (MI), Italy
11/17/2009 President, School PhD Ph.D. Program in Translational and Molecular Medicine " University of Milano-Bicocca, Milan, Italy (www.dimet.org)
Societies
2004-2008 President SIOP Europe
Since 1985 Member of the Italian Group of Cooperation in Immunology
Since 1991 Member of the Italian Society of Experimental Hematology
Since 1992 Member of the American Society of Hematology
Since 1992 Member of the Italian Society of Pediatric Hematology and Oncology (AIEOP)
Since 1997 Member of the International Society of Pediatric Oncology (SIOP)
Since 2003 Member of the EHA Scientific Program Committee
Scientific Journals
- Editorial Board of Pediatric Blood & Cancer and The European Journal of Cancer
- Reviewer of Annals of Oncology, Blood, British Journal of Haematology, European Journal of Cancer, European Journal of Haematology, Genes Chromosomes and Cancer, The Hematology Journal/Haematologica, International Journal of Cancer, Leukemia.
Reviewer for funding programs and site visits of international organisations/agencies
- Cancer Research UK
- Children Oncology Group, USA
- Leukemia Research Fund, UK
- National Cancer Institute/National Institute of Health, USA
- OncoSuisse. Swiss Federation Against Cancer, CH
- Stichting Kindergeneeskunde Kankeronderzoek (SKK), NL
- International Union Against Cancer (UICC), CH
Major research interests
- Molecular characterization of childhood ALL.
- Minimal residual disease in childhood ALL.
- Molecular characterization of the t(15;17) translocation in acute promyelocytic leukemia.
- Molecular cloning of translocations.
- Molecular and biological characterization of JMML.
- Cellular and genetic manipulation of ALL blasts.
- Development of strategies for immunotherapy of BCP-ALL
- Molecular characterization of childhood ALL.
- Minimal residual disease in childhood ALL.
- Molecular characterization of the t(15;17) translocation in acute promyelocytic leukemia.
- Molecular cloning of translocations.
- Molecular and biological characterization of JMML.
- Cellular and genetic manipulation of ALL blasts.
- Development of strategies for immunotherapy of BCP-ALL
Wiemels JL, Cazzaniga G, Daniotti M, Eden OB, Addison GM, Masera G, Saha V, Biondi A, Greaves MF. Prenatal origin of acute lymphoblastic leukemia in children. Lancet 354:1499-1503, 1999
Biondi A, Cimino G, Pieters R, Pui C-O. Biological and therapeutic aspects of infant leukemia. Blood 96:24-33, 2000
Cazzaniga G, Daniotti M, Tosi S, Giudici G, Aloisi A, Pogliani E, Kearney L, Biondi A. The paired box domain gene PAX5 is fused to ETV6/TEL in an acute lymphoblastic leukemia case. Cancer Res. 61:4666-70, 2001.
Biagi E, Bambacioni F, Gaipa G, Casati C, Golay J, Biondi A, Introna M. Efficient lentiviral transduction of primary human acute myelogenous and lymphoblastic leukemia cells. Haematologica. 2001; 86:13-6.
Longoni D., D'Amico G., Gaipa G., Vulcano M., Niemeyer C.M., Allavena P.and Biondi A. Committment of pathological monocytic cells from JMML patients to spontaneously differentiate into dendritic cells. The Hematol. Journal. 2002;3:302-306.
Bonamino M, Serafini M, D'Amico G, Gaipa G, Todisco E, Bernasconi S, Golay J, Biondi A, Introna M. Functional transfer of CD40L gene in human B-cell precursor ALL blasts by second-generation SIN lentivectors. Gene Ther. 2004;11:85-93.
Vigouroux S, Yvon E, Biagi E, Brenner MK. Antigen-induced regulatory T cells. Blood. 2004;104:26-33. D"Amico G., Vulcano M., Bugarin C., Bianchi G., Pirovano G., Bonamino M., Marin V., Allavena P, Biagi E. and Biondi A. CD40 activation of BCP-ALL cells generates IL-10 producing, IL-12 defective APCs that induce allogeneic T-cell anergy. Blood. 2004;104: 744-751.
V. Marin, E. Dander, E. Biagi, M. Introna, G. Fazio, A. Biondi and G. D"Amico. Characterization of in vitro migratory properties of anti-CD19 chimeric receptor-redirected CIK cells for their potential use in B-ALL immunotherapy. Exp Hematol. 2006. 34:1219-1229.
D"Amico G., Bonamino M., Dander E., Marin V., Basso G., Balduzzi A., Biagi E., Biondi A. T cells stimulated by CD40L positive leukemic blasts-pulsed dendritic cells meet optimal functional requirements for adoptive T-cell therapy. Leukemia. 2006;20:2015-24.
Marin V., Kakuda H, Dander E, Imai C, Campana D, Biondi A and D"Amico G. Enhancement Of The Anti-leukemic Activity of Cytokine Induced Killer cells With An Anti-CD19 Chimeric Receptor Delivering a 4-1BB Activating Signal. Exp Hematol. 2007. 35:1388-1397.
Biagi E, Marin V, Giordano Attianese GM, Dander E, D'Amico G, Biondi A. Chimeric T-cell receptors: new challenges for targeted immunotherapy in hematologic malignancies. Haematologica. 2007. 9:381-388.
Salvadè A, Belotti D, Donzelli E, D'Amico G, Gaipa G, Renoldi G, Carini F, Baldoni M, Pogliani E, Tredici G, Biondi A, Biagi E.GMP-grade preparation of biomimetic scaffolds with osteo-differentiated autologous mesenchymal stromal cells for the treatment of alveolar bone resorption in periodontal disease. Cytotherapy. 2007. 9:427-438.
Dander E, Pira GL, Biagi E, Perseghin P, Renoldi G, Gaipa G, Introna M, Marin V, Manca F, Biondi A, D'Amico G. Characterization of migratory activity and cytokine profile of helper and cytotoxic CMV-specific T-cell lines expanded by a selective peptide library. Exp Hematol. 36(4):473-85, 2008.
Fazio G, Palmi C, Rolink A, Biondi A, Cazzaniga G. PAX5/TEL acts as a transcriptional repressor causing down-modulation of CD19, enhances migration to CXCL12, and confers survival advantage in pre-BI cells. Cancer Res. Jan 1;68(1):181-9, 2008
Biondi A, Cimino G, Pieters R, Pui C-O. Biological and therapeutic aspects of infant leukemia. Blood 96:24-33, 2000
Cazzaniga G, Daniotti M, Tosi S, Giudici G, Aloisi A, Pogliani E, Kearney L, Biondi A. The paired box domain gene PAX5 is fused to ETV6/TEL in an acute lymphoblastic leukemia case. Cancer Res. 61:4666-70, 2001.
Biagi E, Bambacioni F, Gaipa G, Casati C, Golay J, Biondi A, Introna M. Efficient lentiviral transduction of primary human acute myelogenous and lymphoblastic leukemia cells. Haematologica. 2001; 86:13-6.
Longoni D., D'Amico G., Gaipa G., Vulcano M., Niemeyer C.M., Allavena P.and Biondi A. Committment of pathological monocytic cells from JMML patients to spontaneously differentiate into dendritic cells. The Hematol. Journal. 2002;3:302-306.
Bonamino M, Serafini M, D'Amico G, Gaipa G, Todisco E, Bernasconi S, Golay J, Biondi A, Introna M. Functional transfer of CD40L gene in human B-cell precursor ALL blasts by second-generation SIN lentivectors. Gene Ther. 2004;11:85-93.
Vigouroux S, Yvon E, Biagi E, Brenner MK. Antigen-induced regulatory T cells. Blood. 2004;104:26-33. D"Amico G., Vulcano M., Bugarin C., Bianchi G., Pirovano G., Bonamino M., Marin V., Allavena P, Biagi E. and Biondi A. CD40 activation of BCP-ALL cells generates IL-10 producing, IL-12 defective APCs that induce allogeneic T-cell anergy. Blood. 2004;104: 744-751.
V. Marin, E. Dander, E. Biagi, M. Introna, G. Fazio, A. Biondi and G. D"Amico. Characterization of in vitro migratory properties of anti-CD19 chimeric receptor-redirected CIK cells for their potential use in B-ALL immunotherapy. Exp Hematol. 2006. 34:1219-1229.
D"Amico G., Bonamino M., Dander E., Marin V., Basso G., Balduzzi A., Biagi E., Biondi A. T cells stimulated by CD40L positive leukemic blasts-pulsed dendritic cells meet optimal functional requirements for adoptive T-cell therapy. Leukemia. 2006;20:2015-24.
Marin V., Kakuda H, Dander E, Imai C, Campana D, Biondi A and D"Amico G. Enhancement Of The Anti-leukemic Activity of Cytokine Induced Killer cells With An Anti-CD19 Chimeric Receptor Delivering a 4-1BB Activating Signal. Exp Hematol. 2007. 35:1388-1397.
Biagi E, Marin V, Giordano Attianese GM, Dander E, D'Amico G, Biondi A. Chimeric T-cell receptors: new challenges for targeted immunotherapy in hematologic malignancies. Haematologica. 2007. 9:381-388.
Salvadè A, Belotti D, Donzelli E, D'Amico G, Gaipa G, Renoldi G, Carini F, Baldoni M, Pogliani E, Tredici G, Biondi A, Biagi E.GMP-grade preparation of biomimetic scaffolds with osteo-differentiated autologous mesenchymal stromal cells for the treatment of alveolar bone resorption in periodontal disease. Cytotherapy. 2007. 9:427-438.
Dander E, Pira GL, Biagi E, Perseghin P, Renoldi G, Gaipa G, Introna M, Marin V, Manca F, Biondi A, D'Amico G. Characterization of migratory activity and cytokine profile of helper and cytotoxic CMV-specific T-cell lines expanded by a selective peptide library. Exp Hematol. 36(4):473-85, 2008.
Fazio G, Palmi C, Rolink A, Biondi A, Cazzaniga G. PAX5/TEL acts as a transcriptional repressor causing down-modulation of CD19, enhances migration to CXCL12, and confers survival advantage in pre-BI cells. Cancer Res. Jan 1;68(1):181-9, 2008
Project Title:
Project Title:
Molecular dissection of the etiopathogenesis of childhood Acute Lymphoblastic Leukemia (ALL)
The pre-leukemic state of the TEL-AML1 positive cell. TEL-AML1 fusion is the most frequent genetic abnormality in paediatric cancer, and it is usually an early or initiating and pre-natal event in childhood ALL. Transformation results in the generation of a persistent pre-leukemic clone, which converts to frank ALL post-natally (at 1-15 years) following the acquisition of secondary genetic alterations. The mechanism by which the transcriptional dysregulation imposed by TEL-AML1 impacts on the pre-leukemic phenotype and disease natural history is unknown. We showed that the TEL-AML1 protein inhibits the TGFb response pathway, facilitating the selective expansion of otherwise more slowly expanding TEL-AML1 expressing progenitors. We aim to further explore the pre-leukemic phase by analyzing the migration/adhesion properties of the TEL-AML1 positive cells, and their interactions with the bone marrow niche. 2) Functional characterization of PAX5 genomic lesions. PAX5 is a transcription factor essential for B-cell development. Recently, it has been found as frequent target of aberrancies in childhood ALL (30% of B-cell ALL cases), showing monoallelic loss, point mutations or chromosomal translocations. The role of these aberrancies is still poorly understood. We reported the first evidence of the PAX5/TEL fusion gene in an ALL patient with the t(9;12) translocation, and we further investigated the molecular and functional roles of PAX5/TEL protein in vitro, in murine wild type preBI cells. In vitro, PAX5/TEL protein has a dominant negative effect on target genes, it interferes with the process of B-cell differentiation and migration; and it induces resistance to apoptosis, key events in the process of B-cell transformation. We aim to further investigate the effect of the PAX5-TEL chimeric protein on the differentiation program of preBI cells, to evaluate the migration/adhesion properties of the PAX5 aberrant cells, and to study the in vivo role of the PAX5-TEL fusion in mice models. We are also characterizing additional PAX5 lesions in childhood ALL patients. 3) Identification and characterization of the �leukemia-initiating stem cell� in Infant ALL with t(4;11). The reciprocal t(4;11), giving rise to the expression of MLL/AF4 fusion protein, is the most frequent aberration involving the MLL gene, and it is mainly associated to infant ALL (less than 12 months old at diagnosis). These patients have an overall a very poor prognosis, and their cells have a peculiar gene signature and phenotype that confer distinct properties to the disease (different form other form of common leukemia), which may be driven and sustained by a unique clone of stem cells. Aim of this task is the identification of the subset of cells responsible for initiating, expanding and maintaining the tumor, the �cancer stem cell� of Infant ALL/t(4;11). Identifying the nature of this cell not only may be key to unravelling the origin and the dismal prognosis of the disease, but also it is crucial to develop new therapies able to target these cells in patients. We started a combined multiparameter immunophenotype and FISH analyses on different subpopulations of PB/BM-derived cells from infant ALL/t(4;11) patients at diagnosis. We will set up an in vitro assay to confirm the clonogenic potential and self-replating ability of these cell. The NOD/SCID repopulating assay, by injecting purified sub-populations, will assess the ability of the candidate leukemia stem cell to transfer the leukemia in vivo.
Project Title:
Chimeric T cells for the treatment of pediatric cancers
Leukemias are the most common cancers affecting children while malignant lymphomas, including non-Hodgkin lymphomas (NHL), comes in third position after brain tumors. A significant number of children with leukemia/lymphomas still fail current therapies. The aim of the CHILDHOPE project is to develop a safe and efficient adoptive immunotherapy for children with advanced or refractory malignancies. CHILDHOPE particularly focuses on three pediatric tumors: acute B-lineage lymphoblastic leukemia, non-hodgkin B-lineage lymphoma and acute myeloid leukemia. The CHILDHOPE project is a new approach in pediatric cancer treatment since it brings from bench to bedside (and back) an innovative technology as yet never applied in children with advanced or refractory hematopoietic malignancies. The CHILDHOPE translational research project will focus on: 1. Improving and testing the efficacy and the safety of anti-leukemia/lymphoma chimeric T cells in relevant preclinical models in vitro and in vivo in mice. 2. Scaling-up this technology to numbers suitable for a clinical application in children with hematopoietic malignancies. Based on biological material obtained from our preclinical models and from children treated with these genetically engineered T cells, dissecting the interface between the host and tumor and immune cells and use this knowledge to understand the mechanisms of anti-tumor action, validate novel targets and diagnostic tools specific to children affected with leukemia or lymphomas. The CHILDHOPE project is built on the excellence of a network of EU-based partners with a broad experience in the field of pediatric hematology and oncology, immunology and cell & gene therapies and integrates the international confederation of parents of children with cancer and an SME specialized in the project management.