The Italian Network for Tumor Biotherapy (NIBIT): Getting together to push the field forward

  • Michele Maio1, 2Email author,

    Affiliated with

    • Hugues JM Nicolay1, 2,

      Affiliated with

      • Paolo Ascierto3,

        Affiliated with

        • Filippo Belardelli4,

          Affiliated with

          • Roberto Camerini5,

            Affiliated with

            • Mario P Colombo6,

              Affiliated with

              • Paola Queirolo7,

                Affiliated with

                • Ruggero Ridolfi8,

                  Affiliated with

                  • Vincenzo Russo9,

                    Affiliated with

                    • Lucia Anzalone1,

                      Affiliated with

                      • Ester Fonsatti1 and

                        Affiliated with

                        • Giorgio Parmiani10

                          Affiliated with

                          Journal of Translational Medicine20086:8

                          DOI: 10.1186/1479-5876-6-8

                          Received: 18 January 2008

                          Accepted: 12 February 2008

                          Published: 12 February 2008

                          Abstract

                          As for a consolidated tradition, the 5th annual meeting of the Italian Network for Cancer Biotherapy took place in the Certosa of Pontignano, a Tuscan monastery, on September 20–22, 2007. The congress gathered more than 40 Italian leading groups representing academia, biotechnology and pharmaceutical industry. Aim of the meeting was to share new advances in cancer bio-immunotherapy and to promote their swift translation from pre-clinical research to clinical applications. Several topics were covered including: a) molecular and cellular mechanisms of tumor escape; b) therapeutic antibodies and recombinant constructs; c) clinical trials up-date and new programs; d) National Cooperative Networks and their potential interactions; e) old and new times in cancer immunology, an "amarcord". Here, we report the main issues discussed during the meeting.

                          Introduction

                          The meeting took place in a monastery built by the Carthusian Order on August 1343, located on the border between the town-states of Florence and Siena. The Certosa of Pontignano preserved through the ages its original atmosphere as an oasis of peace (Fig. 1). Nowadays, the monastery is an University guesthouse where the annual symposium of the NIBIT (acronym for the Network Italiano per la Bioterapia dei Tumori – Italian Network for Tumor Biotherapy) is organized. Tuscan landscape and culinary specialties provided a peace of mind and body that helped to reach the event goals.
                          http://static-content.springer.com/image/art%3A10.1186%2F1479-5876-6-8/MediaObjects/12967_2008_Article_238_Fig1_HTML.jpg
                          Figure 1

                          The Main Cloister of the Certosa of Pontignano (Siena, Italy).

                          The increasing knowledge of the molecular mechanisms involved in neoplastic transformation, of the biology of cancer cells, and of the immunological mechanisms regulating tumor-host interactions allows to identify and to apply novel and eventually more effective bio-immunotherapeutic strategies in cancer patients [1].

                          However, for their optimal clinical development, and for their swift translation from the laboratory to the clinical setting, these new therapeutic approaches require a tight cultural and operative interaction among different professionals involved in the clinical, regulatory and industrial fields [2, 3]. Thus, a shared effort is mandatory in order to evaluate with due appropriateness, rapidity and scientific rigor the biological and clinical efficacy of novel treatments that become available. Nevertheless, while cancer bio-immunotherapy is consolidating its role as an additional and powerful option in the comprehensive treatment of cancer patients, it raises new and specific procedural, ethical, and legal challenges to its broader clinical application. Therefore, the efficient clinical development and application of new modalities of cancer bio-immunotherapy is often difficult for large research entities and in most cases impossible for small research units [4].

                          On these premises, and to cope with a need strongly felt by the Italian academic, industrial and regulatory community, the NIBIT was created in 2004.

                          Main objectives of the NIBIT are

                          1. a)

                            To promote and foster a stronger scientific and operative interaction among professionals belonging to Academia, Biotech/Pharmaceutical Industry, Regulatory Bodies;

                             
                          2. b)

                            To develop innovative, multi-center clinical studies of cancer bio-immunotherapy at national level;

                             
                          3. c)

                            To set-up initiatives to inform patients about potentials and limitations of cancer bio-immunotherapy and on ongoing clinical trials [5].

                             

                          Scientific welcome to the attendees

                          In his scientific welcome address, Lucio Luzzatto (University of Florence), Scientific Director of the Istituto Toscano Tumori, made an excursus on scientific achievements in the fields of human immunogenetics and cancer immunology that are providing the molecular basis and the scientific rationale to implement novel and eventually more effective immunotherapeutic strategies in cancer patients.

                          Molecular and cellular mechanisms of tumor escape (Chairs: Paola Zanovello and Paola Nisticò)

                          The presentation of Francesca Fallarino (University of Perugia) focused on "Tumor escape from effector T cells" and the immunoregulatory enzyme indoleamine 2,3 dioxygenase (IDO). IDO has been associated with a wide variety of human cancers because of its ability to potentiate suppressing regulatory T-cells (T-regs) functions through the catabolism of the essential aminoacid tryptophan. Additionally, it has been recently demonstrated that IDO acts not only as an effector mechanisms of T-regs but also represents a way to generate new T-regs. These findings underscore the importance of the clinical development of IDO inhibitors for suppressing cancer progression [6].

                          Susanna Mandruzzato (University of Padua) presented her experience in "Myeloid-derived suppressor cells: from mouse to humans". Myeloid-derived suppressor cells (MDSC) represent a population of myelo-monocytic cells lacking the markers of mature myeloid cells and expressing both Gr-1 and CD11b in mice. MDSCs bear a high potential to suppress immune responses both in vitro and in vivo. Mandruzzato showed that even if human MDSC equivalents are not entirely known, granulocyte subpopulations might be involved [7].

                          Epigenetic modifications generate heritable changes in the expression of single genes or patterns of genes not based on structural changes of the DNA sequence. Luca Sigalotti (Centro di Riferimento Oncologico, Aviano) in his presentation "Epigenetic intervention in tumor escape mechanisms" demonstrated that hypomethylating agents can modulate the expression of Cancer Testis Antigens and their presentation on the cell surface of neoplastic cells, as well as HLA class I antigens, leading to a more efficient recognition of melanoma cells by cytotoxic T cells (CTL) [8].

                          Licia Rivoltini (Istituto Nazionale Tumori, Milan) discussed on "Myeloid suppressor cells in melanoma patients", reporting that microvesicles or exosomes released by tumor cells and purified from patients' plasma induce CD14+ HLA-DRlow cells with TGF-β-mediated suppressive activity. Therefore, blocking their release by neoplastic cells could improve immune recognition of cancer cells [9].

                          Tumor-released factors targeting nuclear receptors of dendritic cells (DC) impair DC migration. Along this line, Eduardo J. Villablanca (San Raffaele Scientific Institute, Milan) discussed on "Impairment of DC migration by tumor-released factors targeting DC nuclear receptors" pointing out that the expression of chemokine receptor CCR7, that guides mature DC from peripheral tissues to lymphoid compartments, is inhibited on DC by soluble factors released from 50% of the melanoma cells investigated in vitro.

                          Conclusion

                          During the 5th meeting of the NIBIT, scientists representing academia, biotechnology and pharmaceutical industry put together their ideas, results and their good will to make real translational cancer biotherapy. Here, we insist on the necessity to continue and strengthen this collaboration both nationally and internationally, [37] and we invite basic scientist, clinical researchers and industries to contact us and join the network to overstep obstacles in cancer care improvement [38].

                          Declarations

                          Acknowledgements

                          The cost of the article processing charge is covered by the Italian Network for Cancer Biotherapy.

                          Authors’ Affiliations

                          (1)
                          Division of Medical Oncology and Immunotherapy, Department of Oncology, Istituto Toscano Tumori, University Hospital of Siena
                          (2)
                          Cancer Bioimmunotherapy Unit, Department of Medical Oncology, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico
                          (3)
                          Unit of Clinical Immunology, Istituto Nazionale Tumori "Fondazione Pascale"
                          (4)
                          Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità
                          (5)
                          Clinical Research Unit III, Sigma Tau SpA
                          (6)
                          Immunotherapy and Gene Therapy Unit, Department of Experimental Oncology, Fondazione Istituto Ricovero e Cura a Carattere Scientifico Istituto Nazionale dei Tumori
                          (7)
                          Department of Medical Oncology A, National Institute for Cancer Research
                          (8)
                          Immunotherapy and Somatic Cell Therapy Unit, Istituto Scientifico Romagnolo per lo studio e la cura dei tumori
                          (9)
                          Cancer Gene Therapy Unit, Department of Oncology, Scientific Institute S. Raffaele
                          (10)
                          Department of Oncology, San Raffaele Scientific Institute

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                          Copyright

                          © Maio et al. 2008

                          This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​2.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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