Federica Cavallo

Azienda Ospedaliera Città della Salute e della Scienza di Torino, Torino, Piedmont, Italy

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Publications (193)947.66 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Ultrasound (US)-activated perfluoropentane-cored oxygen-loaded nanobubbles (OLNBs) were recently proposed as adjuvant therapeutic tools for pathologies of different etiology sharing hypoxia as a common feature (e.g. diabetes-associated chronic wounds, anaerobic infections, cancer). Here we introduce a new platform of oxygen nanocarriers, constituted of 2H,3H-decafluoropentane (DFP) as core fluorocarbon and chitosan as shell polysaccharide, and available either in liquid or gel formulations. Such oxygen-loaded nanodroplets (OLNDs) display spherical morphology, 700 nm diameters, cationic surfaces, good oxygen carrying capacity (without singlet oxygen generation after sterilization by ultraviolet-C rays), and no toxic effects on human keratinocytes. In vitro, OLNDs are more effective in releasing oxygen to hypoxic environments than former OLNBs, either with or without complementary US administration (f = 1 MHz; P = 5 W). In vivo, sonication of topically applied OLNDs appears essential to allow significant and time-sustained oxygen release. Taken together, the present data suggest that US-activated chitosan-shelled/DFP-cored OLNDs might be innovative, suitable and cost-effective devices to treat several hypoxia-associated pathologies of the cutaneous tissues.
    RSC Advances 08/2014; 4(72). · 2.56 Impact Factor
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    ABSTRACT: PCR-based minimal residual disease (MRD) analysis is a useful prognostic tool in multiple myeloma (MM), although its long-term impact still needs to be addressed. This report presents the updated results of the GIMEMA-VEL-03-096 trial. Thirty-nine MM patients receiving bortezomib-thalidomide-dexamethasone after autologous transplantation were monitored for MRD by both nested and real-time quantitative (RQ)-PCR until relapse. Our data confirm the strong impact of MRD on survival: OS was 72% at 8-years median follow-up for patients in major MRD response versus 48% for those experiencing MRD persistence (P=0.041). In addition, MRD kynetics resulted predictive for relapse: indeed median remission duration was not reached for patients in major MRD response, 38 months for those experiencing MRD reappearance and 9 months for patients with MRD persistence (p<0.001). Moreover: 1) the 26 patients achieving major MRD response (67%) benefit of excellent disease control (median TNT: 42 months); 2) MRD reappearance heralds relapse, with a TNT comparable to that of MRD persistence (9 versus 10 months, P=0.706); 3) the median lag between MRD reappearance and need for salvage treatment is 9 months. These results suggest a long-term MRD monitoring in MM patients and the need for maintenance or pre-emptive treatments ensuring durable responses.Leukemia accepted article preview online, 16 July 2014; doi:10.1038/leu.2014.219.
    Leukemia. 07/2014;
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    ABSTRACT: Purpose: Due to the many similarities with its human counterpart, canine (c) malignant melanoma (MM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety and therapeutic efficacy of a human (h) chondroitin sulfate proteoglycan-4 (CSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at over 80% provides the rationale for using a hCSPG4 DNA vaccine in the cMM model. Experimental Design: Dogs with stage II-III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration which was followed immediately by electroporation (electrovaccination) for at least six, and up to twenty, months. The immunogenicity, safety and therapeutic efficacy of the vaccine have been evaluated. Results: hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared to 13 non-vaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T cell response and only two gave a detectable interferon (IFN)-γ response. Conclusion: Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the "self" antigen and appears to be effective in treating cMM, laying the foundation for its translation to a human clinical setting.
    Clinical cancer research : an official journal of the American Association for Cancer Research. 05/2014;
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    ABSTRACT: The antitumor activity induced by intratumoral vaccination with poxvirus expressing a tumor antigen was shown to be superior to that induced by subcutaneous vaccination. Salivary gland carcinomas overexpress ErbB2. Trastuzumab, a monoclonal antibody to ErbB2, was proposed for salivary gland tumors treatment. We explored the effectiveness of intratumoral vaccination with the recombinant vaccinia virus ErbB2/neu (rV-neuT) vaccine in hampering the growth of transplanted Neu-overexpressing BALB-neuT salivary gland cancer cells (SALTO) in BALB-neuT mice.
    Journal of translational medicine. 05/2014; 12(1):122.
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    ABSTRACT: Non-small cell lung cancer (NSCLC) accounts for 81% of all cases of lung cancer and they are often fatal because 60% of the patients are diagnosed at an advanced stage. Besides the need for earlier diagnosis, there is a high need for additional effective therapies. In this work, we investigated the feasibility of a lung cancer progression mouse model, mimicking features of human aggressive NSCLC, as biological reservoir for potential therapeutic targets and biomarkers.
    BMC genomics. 05/2014; 15(Suppl 3):S1.
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    ABSTRACT: Perforin (pfp)-mediated cytotoxicity is one of the principal immunosurveillance mechanisms involved in the fight against cancer. However, its importance in spontaneous epithelial cancer is still poorly defined. In this study, we use a realistic mouse model that displays many features that are equivalent to human pathology to evaluate the role of pfp-dependent immunosurveillance by comparing tumor progression in rat ERBB-2 (neu) transgenic, pfp-proficient (neu(+)/pfp(+)) or pfp-deficient (neu(+)/pfp(-)) BALB/c male mice. Adult neu(+)/pfp(+) males developed poorly differentiated salivary carcinomas, whereas neu(+)/pfp(-) males displayed their salivary carcinomas noticeably earlier and showed zones of more highly differentiated tumor, indicating that pfp-mediated immunosurveillance is able not only to delay the growth kinetic of an aggressive epithelial tumor, but also to shape its histology. The role of pfp-mediated immunosurveillance appeared to be of even more dramatic importance against the less aggressive male mammary carcinomas. In neu(+)/pfp(+) males, the incidence of mammary carcinomas was a sporadic and late event. In contrast, in neu(+)/pfp(-) males their incidence was four-fold higher. This higher cancer incidence was associated with a 2-fold higher occurrence of persisting mammary remnants, a major risk factor for mammary cancer in male mice, and one that would appear to be due to pfp's previously unidentified involvement in male mammary gland rejection during embryogenesis. This work thus provides further proof of the complex role that the immune system plays in the body and gives new insight into the pathogenesis of epithelial tumors, demonstrating that the penetrance and malignancy of a tumor may be dramatically affected by pfp-dependent mechanisms.
    The Journal of Immunology 04/2014; · 5.52 Impact Factor
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    ABSTRACT: Perforin (pfp)-mediated cytotoxicity is one of the principal immunosurveillance mechanisms involved in the fight against cancer. However, its importance in spontaneous epithelial cancer is still poorly defined. In this study, we use a realistic mouse model that displays many features that are equivalent to human pathology to evaluate the role of pfp-dependent immunosurveillance by comparing tumor progression in rat ERBB-2 (neu) transgenic, pfp-proficient (neu+/pfp+) or pfp-deficient (neu+/pfp-) BALB/c male mice. Adult neu+/pfp+ males developed poorly differentiated salivary carcinomas, whereas neu+/pfp- males displayed their salivary carcinomas noticeably earlier and showed zones of more highly differentiated tumor, indicating that pfp-mediated immunosurveillance is able not only to delay the growth kinetic of an aggressive epithelial tumor, but also to shape its histology. The role of pfp-mediated immunosurveillance appeared to be of even more dramatic importance against the less aggressive male mammary carcinomas. In neu+/pfp+ males, the incidence of mammary carcinomas was a sporadic and late event. In contrast, in neu+/pfp- males their incidence was four-fold higher. This higher cancer incidence was associated with a 2-fold higher occurrence of persisting mammary remnants, a major risk factor for mammary cancer in male mice, and one that would appear to be due to pfp's previously unidentified involvement in male mammary gland rejection during embryogenesis. This work thus provides further proof of the complex role that the immune system plays in the body and gives new insight into the pathogenesis of epithelial tumors, demonstrating that the penetrance and malignancy of a tumor may be dramatically affected by pfp-dependent mechanisms.
    The Journal of Immunology 04/2014; · 5.52 Impact Factor
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    ABSTRACT: Despite the great success of HER2 vaccine strategies in animal models, effective clinical results have not yet been obtained. We studied the feasibility of using DNA coding for chimeric rat/human HER2 as a tool to break the unresponsiveness of T cells from patients with HER2-overexpressing tumors (HER2-CP) EXPERIMENTAL DESIGN: Dendritic cells (DCs) generated from patients with HER2-overexpressing breast (n=28) and pancreatic (n=16) cancer were transfected with DNA plasmids that express human HER2 or heterologous rat sequences in separate plasmids or as chimeric constructs encoding rat/human HER2 fusion proteins and used to activate autologous T cells. Activation was evaluated by IFN-γ ELISpot assay, perforin expression, and ability to halt HER2+ tumor growth in vivo. Specific sustained proliferation and IFN-γ production by CD4 and CD8 T cells from HER2-CP was observed after stimulation with autologous DC transfected with chimeric rat/human HER2 plasmids. Instead, T cells from healthy donors (n=22) could be easily stimulated with autologous DCs transfected with any human, rat or chimeric rat/human HER2 plasmid. Chimeric HER-2-transfected DCs from HER2-CP were also able to induce a sustained T cell response that significantly hindered the in vivo growth of HER2+-tumors. The efficacy of chimeric plasmids in overcoming tumor-induced T cell dysfunction relies on their ability to circumvent suppressor effects exerted by Treg cells and/or IL-10 and TGF-β1. These results provide the proof of concept that chimeric rat/human HER2 plasmids can be used as effective vaccines for any HER2-CP with the advantage of being not limited to specific MHC.
    Clinical Cancer Research 03/2014; · 7.84 Impact Factor
  • Cancer Immunology and Immunotherapy 03/2014; · 3.64 Impact Factor
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    ABSTRACT: Multiple myeloma is still an incurable disease with pattern of regression and remission followed by multiple relapses raising from the residual myeloma cells surviving even in the patients who achieve complete clinical response to treatment. New antimyeloma drugs such as thalidomide, lenalidomide, and bortezomib have dramatically changed treatment paradigm leading to both tumor reduction and tumor suppression. Much progress has been made, but still many unsolved questions remain. In the mode of sequencing treatment for patients with multiple myeloma, we are still using old drugs such as the alkylating agent melphalan, which continues to play a central role in the transplantation setting. Newer drugs are now emerging and are being tested: monoclonal antibodies, histone deacetylase (romidespsin), MLN9708 (ixazomib) a new oral proteasome inhibitor, carfilzomib, signal transduction modulator perifosine. Many advances have been made, but there is still a long way to go.
    Current Treatment Options in Oncology 03/2014; · 2.42 Impact Factor
  • Seminars in Oncology 02/2014; 41(1):e1-9. · 4.33 Impact Factor
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    ABSTRACT: Abnormal activation of MET/HGF (Hepatocyte Growth Factor) pathway has been described in several tumours and increased HGF plasmatic levels have been detected in patients with aggressive multiple myeloma (MM). MET and HGF mRNA expression was investigated in 105 samples of purified plasma cells derived from newly diagnosed MM patients treated with bortezomib-based induction therapy. Gene expression was compared with response to therapy and clinical outcome. MET gene copy number was also evaluated. MET mRNA expression was higher in CD138(+) than in CD138(-) cells (median 76·90 vs. 11·24; P = 0·0009). Low MET mRNA expression characterized patients with better response (complete response or very good partial response) compared to other patients (median 56·10 vs. 134·83; P = 0·0006). After a median follow-up of 50 months, patients with high MET mRNA expression displayed a worse progression-free survival (PFS; P = 0·0029) and overall survival (OS; P = 0·0023) compared to those with low MET mRNA levels. Patients with both high MET mRNA expression and high β2-microglobulin level (>5·5 mg/l) had further worse median PFS (P < 0·0001) and OS (P < 0·0001). Patients carrying 4 MET gene copies (8 out of 82, 9·8%) also had a short PFS. High MET mRNA expression identifies patients with dismal PFS and OS and the combination with high β2-microglobulin further characterizes patients with worse outcome.
    British Journal of Haematology 01/2014; · 4.94 Impact Factor
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    ABSTRACT: The availability of mice transgenic for the human HER2 gene (huHER2) and prone to the development of HER2-driven mammary carcinogenesis (referred to as FVB-huHER2 mice) prompted us to study active immunopreventive strategies targeting the human HER2 molecule in a tolerant host. FVB-huHER2 were vaccinated with either IL-12-adjuvanted human HER2-positive cancer cells or DNA vaccine carrying chimeric human-rat HER2 sequences. Onset and number of mammary tumors were recorded to evaluate vaccine potency. Mice sera were collected and passively transferred to xenograft-bearing mice to assess their antitumor efficacy. Both cell and DNA vaccines significantly delayed tumor onset, leading to about 65% tumor-free mice at 70 weeks, whereas mock-vaccinated FVB-huHER2 controls developed mammary tumors at a median age of 45 weeks. In the DNA vaccinated group, 65% of mice were still tumor-free at about 90 weeks of age. The number of mammary tumors per mouse was also significantly reduced in vaccinated mice. Vaccines broke the immunological tolerance to the huHER2 transgene, inducing both humoral and cytokine responses. The DNA vaccine mainly induced a high and sustained level of anti-huHER2 antibodies, the cell vaccine also elicited interferon (IFN)-gamma production. Sera of DNA-vaccinated mice transferred to xenograft-carrying mice significantly inhibited the growth of human HER2-positive cancer cells. Anti-huHER2 antibodies elicited in the tolerant host exert antitumoral activity.
    Breast cancer research: BCR 01/2014; 16(1):R10. · 5.87 Impact Factor
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    ABSTRACT: We have recently demonstrated that a DNA vaccine targeting membrane-bound KIT ligand (KITL) inhibits tumor growth by interfering with vessel stabilization/permeability and by disrupting the recruitment of inflammatory cells and regulatory T cells, the latter being an essential mechanism by which tumors resist available treatments. Combining KITL-targeting vaccines with conventional chemotherapy might avert drug resistance and improve the efficacy of standard-of-care therapeutic interventions.
    Oncoimmunology. 01/2014; 3(1):e27259.
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    ABSTRACT: The tyrosine kinase human epidermal growth factor receptor 2 (HER2) gene is amplified in approximately 20% of human breast cancers and is associated with an aggressive clinical course and the early development of metastasis. Its crucial role in tumor growth and progression makes HER2 a prototypic oncoantigen, the targeting of which may be critical for the development of effective anticancer therapies. The setup of anti-HER2 targeting strategies has revolutionized the clinical outcome of HER2(+) breast cancer. However, their initial success has been overshadowed by the onset of pharmacological resistance that renders them ineffective. Since the tumor microenvironment (TME) plays a crucial role in drug resistance, the design of more effective anticancer therapies should depend on the targeting of both cancer cells and their TME as a whole. In this review, starting from the successful know-how obtained with a HER2(+) mouse model of mammary carcinogenesis, the BALB-neuT mice, we discuss the role of TME in mammary tumor development. Indeed, a deeper knowledge of antigens critical for cancer outbreak and progression and of the mechanisms that regulate the interplay between cancer and stromal cell populations could advise promising ways for the development of the best anticancer strategy.
    BioMed Research International 01/2014; 2014:534969. · 2.88 Impact Factor
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    ABSTRACT: Vaccines against human breast cancer are an unfulfilled promise. Despite decades of promising preclinical and clinical research, no vaccine is currently available for breast cancer patients. Preclinical research has much to do with this failure, as early mouse models of mammary carcinoma did not mirror the molecular, cellular, antigenic and immunological features of human breast cancer. The advent of HER-2 transgenic mice gave impulse to a new generation of cell and DNA vaccines against mammary carcinoma, that in turn led to the definition of significant antigenic (oncoantigens) and cellular (cancer-initiating cells, preneoplastic lesions, incipient metastases) targets. Future preclinical developments will include the discovery of novel oncoantigens in HER-2-negative mammary carcinoma and the targeting of activated HER-2 molecular variants. Translation to clinically effective vaccines will be fostered not only by new preclinical model systems, but also by the possibility to conduct veterinary vaccination trials in companion animals.
    Expert Review of Vaccines 12/2013; 12(12):1449-63. · 4.22 Impact Factor
  • Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 10/2013; · 10.16 Impact Factor
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    ABSTRACT: A functional c-Kit/Kit ligand (KitL) signalling network is required for tumour angiogenesis and growth, and therefore the c-Kit/KitL system might well be a suitable target for the cancer immunotherapy approach. We herein describe a strategy that targets membrane-bound KitL (mbKitL) via DNA vaccination. The vaccination procedure generated antibodies which are able to detect mbKitL on human tumour endothelial cells (TECs) and on the breast cancer cell line: TSA. DNA vaccination, interferes with tumour vessel formation and transplanted tumour growth in vivo. Histological analysis demonstrates that, while tumour cell proliferation and vessel stabilisation are impaired, vessel permeability is increased in mice that produce mbKitL-targeting antibodies. We also demonstrate that vessel stabilisation and tumour growth require Akt activation in endothelial cells but not in pericytes. Moreover, we found that regulatory T cells (Treg) and tumour infiltrating inflammatory cells, involved in tumour growth and angiogenesis, were reduced in number in the tumour microenvironment of mice that generate anti-mbKitL antibodies. These data provide evidence that mbKitL targeted vaccination is an effective means of inhibiting tumour angiogenesis and growth.
    European journal of cancer (Oxford, England: 1990) 10/2013; · 4.12 Impact Factor
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    ABSTRACT: Lactoferrin, a key component of innate immunity, is a cationic monomeric 80-kDa glycoprotein of the transferrin superfamily. Recombinant human lactoferrin, known as talactoferrin (TLF), induces a distinct functional maturation program in human dendritic cells (DCs) derived from peripheral blood monocytes. However, the receptors and molecular mechanisms involved in this induction have not been fully determined. By exploiting genome-wide transcription profiling of immature DCs, TNF-α- and IL-1β-matured DCs (m-DCs), and TLF-matured DCs (TLF-DCs), we have detected a set of transcripts specific for m-DCs and one specific for TLF-DCs. Functional network reconstruction highlighted, as expected, the association of m-DC maturation with IL-1β, TNF-α, and NF-κB, whereas TLF-DC maturation was associated with ERK and NF-κB. This involvement of ERK and NF-κB transduction factors suggests direct involvement of Toll-like receptors (TLRs) in TLF-induced maturation. We have used MyD88 inhibition and siRNA silencing TLRs on human DCs and mouse TLR-2-knockout cells, to show that TLF triggers the maturation of both human and mouse DCs through TLR-2 and TLR-4.-Spadaro, M., Montone, M., Arigoni, M., Cantarella, D., Forni, G., Pericle, F., Pascolo, S., Calogero, R. A., Cavallo, F. Recombinant human lactoferrin induces human and mouse dendritic cell maturation via Toll-like receptors 2 and 4.
    The FASEB Journal 10/2013; · 5.70 Impact Factor
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    ABSTRACT: Multiple myeloma is a highly treatable but still incurable malignancy. Many advances have been made in the treatment of this disease, particularly thanks to the introduction of the immunomodulatory drugs, thalidomide and lenalidomide, and the proteasome inhibitor, bortezomib. Different trials have supported the inclusion of consolidation/maintenance therapy as part of a sequential approach after induction therapy and transplantation (for eligible patients). This therapeutic strategy aims to maintain or even improve response obtained after induction, and ultimately to prolong survival. The role of consolidation/maintenance therapy has been assessed in patients eligible and ineligible for transplantation, and proved to be a valuable option. The improved outcome reported with consolidation/maintenance therapy should, however, be balanced against the toxicity profile of such an approach. Prolonged exposure to a drug might in fact increase toxicity, and prompt management of adverse events is necessary.
    Clinical lymphoma, myeloma & leukemia 09/2013; 13 Suppl 2:S349-54.

Publication Stats

4k Citations
947.66 Total Impact Points

Institutions

  • 2009–2014
    • Azienda Ospedaliera Città della Salute e della Scienza di Torino
      • Division of Hematology
      Torino, Piedmont, Italy
  • 1991–2014
    • Università degli Studi di Torino
      • • Molecular Biotechnology Center
      • • Department of Medical Science
      • • Dipartimento di Scienze Cliniche e Biologiche
      Torino, Piedmont, Italy
  • 1996–2013
    • University of Bologna
      • Department of Experimental, Diagnostic and Specialty Medicine DIMES
      Bolonia, Emilia-Romagna, Italy
  • 2012
    • Azienda Ospedaliero - Universitaria "Ospedali Riuniti" Trieste
      Trst, Friuli Venezia Giulia, Italy
  • 1994–2012
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      Chieta, Abruzzo, Italy
  • 2007
    • Ospedale San Giovanni Battista, ACISMOM
      Torino, Piedmont, Italy
  • 2006
    • IRCCS Ospedale Casa Sollievo della Sofferenza
      • Hematopoietic Stem Cell Transplantation Centre
      Giovanni Rotondo, Apulia, Italy