Paolo Dellabona
Paolo Dellabona
affiliation: San Raffaele Scientific Institute
research area(s): Experimental Medicine, Immunity And Infection
Course: Basic and Applied Immunology
University/Istitution: Università Vita-Salute San Raffaele
Curriculum Studiorum
1978-1983: Medical Degree, University of Torino, Italy.
1985-1989: Ph.D. in Human Genetics, University of Torino, Italy
1983: Licensed from the Italian Medical Board.
1985-86: Post-doctoral fellow in the laboratory of Fabio Malavasi at the Dipartimento di Genetica, Biologia and Chimica Medica of the University of Torino. Production and use of bi-specific monoclonal antibodies for therapy, diagnosis and basic biology.
1986-87: Post-doctoral fellow in the laboratory of Roberto Accolla at the Ludwig Institute for Cancer Research, Lausanne, Switzerland. Developmentally controlled expression of MHC class II molecules in B cells.
1988-90: Post-doctoral fellow in the laboratory of Christophe Benoist and Diane Mathis at the C.N.R.S.-L.G.M.E/ U.184 ISERM, Medical Faculty, Strasbourg, France. Structure/function relationship of the MHC class II molecules.
1990-92: Member of the Basel Institute for Immunology, Basel, Switzerland. Identification of CD1-restricted T and NKT cells with Giulia Casorati and Antonio Lanzavecchia.
1993-present: Joint Head with Giulia Casorati of the Experimental Immunology Unit, DIBIT, H. San Raffaele Scientific Institute, Milano, Italy.
1998-2009: Coordinator, Cancer Immunotherapy and Gene Therapy Program, San Raffaele Scientific Institute, Milano, Italy.
2009-present: Co-director of the Program of Immunology and Bio-Immuno therapy of Cancer, San Raffaele Scientific Institute, Milano, Italy.

- Studying the development of lipid-specific CD1-restricted T cells and their role in the immune response.
- Defining spontaneous and therapeutically induced tumour-specific T cell responses in cancer patients.
1. de Lalla C, Lepore M, Piccolo FM, Rinaldi A, Scelfo A, Garavaglia C, Mori L, De Libero G, Dellabona P, Casorati G. High-frequency and adaptive-like dynamics of human CD1 self-reactive T cells. Eur J Immunol. 2010 Nov 30. doi: 10.1002/eji.201041211. [Epub ahead of print]
2. de Lalla C, Rinaldi A, Montagna D, Azzimonti L, Bernardo ME, Sangalli LM, Paganoni AM, Maccario R, Di Cesare-Merlone A, Zecca M, Locatelli F, Dellabona P, Casorati G. Invariant NKT Cell Reconstitution in Pediatric Leukemia Patients Given HLA-Haploidentical Stem Cell Transplantation Defines Distinct CD4+ and CD4- Subset Dynamics and Correlates with Remission State. J Immunol. 2011 Feb 25
3. Dellabona P, Casorati G, de Lalla C, Montagna D, Locatelli F. On the use of donor-derived iNKT cells for adoptive immunotherapy to prevent leukemia recurrence in pediatric recipients of HLA haploidentical HSCT for hematological malignancies. Clin Immunol. 2010 Dec 23. [Epub ahead of print]
4. Bellone M, Ceccon M, Grioni M, Jachetti E, Calcinotto A, Napolitano A, Freschi M, Casorati G@, Dellabona P@. iNKT cells control mouse spontaneous carcinoma independently of tumor-specific cytotoxic T cells. PLoS One. 2010 Jan 13;5(1):e8646.
5. Fedeli M, Napolitano A, Wong MP, Marcais A, de Lalla C, Colucci F, Merkenschlager M, Dellabona P@, Casorati G@. Dicer-Dependent MicroRNA Pathway Controls Invariant NKT Cell Development. J Immunol. 2009 Aug 15;183(4):2506-12 Jul 22.
6. Locci M, Draghici E, Marangoni F, Bosticardo M, Catucci M, Aiuti A, Cancrini C, Marodi L, Espanol T, Bredius RG, Thrasher AJ, Schulz A, Litzman J, Roncarolo MG, Casorati G, Dellabona P, Villa A. The Wiskott-Aldrich syndrome protein is required for iNKT cell maturation and function.J Exp Med. 2009 Apr 13;206(4):735-42.
7. Tonti E, Galli G, Malzone C, Abrignani S, Casorati G@, Dellabona P@. NKT cell help to B lymphocytes can occur independently of cognate interaction. Blood. 2009 Jan 8;113(2):370-6.
8. Exley MA, Hou R, Shaulov A, Tonti E, Dellabona P, Casorati G, Akbari O, Akman HO, Greenfield EA, Gumperz JE, Boyson JE, Balk SP, Wilson SB. Selective activation, expansion, and monitoring of human iNKT cells with a monoclonal antibody specific for the TCR alpha-chain CDR3 loop. Eur J Immunol. 2008 Jun;38(6):1756-66.
9. de Lalla C, Festuccia N, Albrecht I, Chang HD, Andolfi G, Benninghoff U, Bombelli F, Borsellino G, Aiuti A, Radbruch A, Dellabona P, Casorati G. Innate-Like Effector Differentiation of Human Invariant NKT Cells Driven by IL-7. J Immunol. 2008 Apr 1;180(7):4415-24.
10. Thedrez A, de Lalla C, Allain S, Zaccagnino L, Sidobre S, Garavaglia C, Borsellino G, Dellabona P@, Bonneville M, Scotet E, Casorati G@. CD4 engagement by CD1d potentiates activation of CD4+ invariant NKT cells. Blood. 2007 Jul 1;110(1):251-8.
11. Galli G, Pittoni P, Tonti E, Malzone C, Uematsu Y, Tortoli M, Maione D, Volpini G, Finco O, Nuti S, Tavarini S, Dellabona P, Rappuoli R, Casorati@ G, Abrignani S. Invariant NKT cells sustain specific B cell responses and memory. Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):3984-9.
12. De Libero G, Macdonald HR, Dellabona P. T cell recognition of lipids: quo vadis? Nat Immunol. 2007 Mar;8(3):223-7
13. Montagna D, Maccario R, Locatelli F, Montini E, Pagani S, Bonetti F, Daudt L, Turin I, Lisini D, Garavaglia C, Dellabona P@, Casorati G@. Emergence of antitumor cytolytic T cells is associated with maintenance of hematologic remission in children with acute myeloid leukemia. Blood. 2006 Dec 1;108(12):3843-50.
Project Title:
Mechanisms of immune surveillance of prostate cancer by CD1d-restricted iNKT cells.
The immune system plays an important role in eradicating malignant cells, a process
called immune surveillance. Invariant natural killer T (iNKT) cells are a unique subset
of T lymphocytes that display innate effector functions and recognize lipid antigens
presented by the CD1d molecule. We have found that in transgenic adenocarcinoma
of the mouse prostate (TRAMP) mice, a pre-clinical model of spontaneous prostate
cancer (PC) that mimics the human pathology, iNKT cells significantly protect against
PC growth. Furthermore, it has been shown that patients with PC exhibit, upon
disease progression, a significant reduction of circulating iNKT cells producing IFNγ,
lending support to the concept that that iNKT cells play an important role in the
immune surveillance of PC.
Clear mechanistic insights into the anti-tumor activity of iNKT cells and the possible
causes that lead to their suppression upon cancer progression are missing. Main
objective of this project is to gain a deeper understanding of the mechanisms by
which iNKT cells control the PC growth, through the following specific aims: 1.
Definition of the direct and/or indirect mechanisms by which iNKT cells control PC cell
growth in TRAMP mice; 2. Definition of the effects of iNKT cell adoptive
immunotherapy on the natural history of PC in TRAMP mice; 3. Characterization of
the global gene expression profile of PC cells and their microenvironment obtained
from TRAMP mice +/- iNKT cells, and correlation of the expression of the relevant
mouse targets in the human prostate tumors.
Investigating this model may hold the key to decipher the molecular pathways by
which the dynamic interactions undergoing between iNKT cells, PC cells and
microenvironment result in the surveillance or the escape of the tumor, and may also
provide new molecular targets that can be harnessed in the design of improved
immunotherapy approaches for PC

Project Title:
Definition of the somatically mutated T cell-defined antigen landscape of colorectal cancer
Colorectal cancer (CRC) is the second cause of cancer death in the Western countries
and responds poorly to conventional therapies. CRCs contain �cancer stem cells�
(CSC), the tumorigenic cell population that maintains cancer growth. Targeting CSC
might improve therapeutic responses in CRC. Immunotherapy is a promising
strategy to selectively attack cancer via harnessing tumor-specific immune
responses. Transformed cells express proteins different from normal tissues that can
be recognized as tumor-associated antigens (TAAs) by the host immune system.
There are different types of TAAs: unique ones result from the random mutagenesis
of cancer genes that introduces non-synonymous somatic mutations in the encoded
proteins. Evidence in mouse models and patients suggest that unique TAAs elicit
strong and specific anti-tumor immune responses. State of the art massive DNA
sequencing allows now to determine the complete genomic sequence of cancer cells
in affordable time and costs, enabling to identify somatically mutated TAAs in any
cancer. Objective of this project is to test the hypothesis that somatic mutations in
CRCs, and possibly also in their CSCs, generate strongly immunogenic TAAs that
elicit tumor-specific responses in patients and could form the basis for vaccines with
improved efficacy. We have delineated a reverse immunology strategy to identify
somatically mutated TAAs in a highly comprehensive way based on: i whole exome
next generation sequencing to define patient-specific non-synonymous mutations in
CRC cells and in their CSC components; ii. bioinformatic prediction of putative
mutated neo-antigenic peptide(s) binding each patient�s HLA alleles; iii analysis of
the T cell responses specific for the mutated peptides in each CRC patient. Overall,
this approach is expected to provide a new conceptual framework for individual
patient-oriented cancer immunotherapy