Federica Cavallo

Università degli Studi di Torino, Torino, Piedmont, Italy

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Publications (227)1314.7 Total impact

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    ABSTRACT: Non-Small Cell Lung Cancer (NSCLC) harboring Anaplastic Lymphoma Kinase (ALK) gene rearrangements is successfully treated with ALK tyrosine kinase inhibitors (TKIs) for only a limited amount of time as most cases relapse due to the development of drug resistance. Here we show that a vaccine against ALK induced a strong and specific immune response that impaired the growth of ALK-positive lung tumors in mouse models prophylactically and therapeutically. The ALK vaccine was efficacious also in combination with ALK TKI treatment and significantly delayed tumor relapses after TKI suspension. Furthermore, we demonstrated that ALK-rearranged lung tumors induce an immunosuppressive microenvironment and that oncogenic ALK regulates the expression of PD-L1 on the surface of lung tumor cells. High PD-L1 expression reduced ALK vaccine efficacy that, however, was restored by administration of anti-PD-1 antibody. Thus, combination of ALK vaccine with TKIs and immune checkpoint blockade therapy might represent a powerful strategy for the treatment of ALK-driven NSCLC.
    09/2015; DOI:10.1158/2326-6066.CIR-15-0089
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    ABSTRACT: Years of unsuccessful attempts at fighting established tumors with vaccines have taught us all that they are only able to truly impact patient survival when used in a preventive setting, as would normally be the case for traditional vaccines against infectious diseases. While true primary cancer prevention is still but a long-term goal, secondary and tertiary prevention are already in the clinic and providing encouraging results. A combination of immunopreventive cancer strategies and recently approved checkpoint inhibitors is a further promise of forthcoming successful cancer disease control, but prevention will require a considerable reduction of currently reported toxicities. These considerations summed with the increased understanding of tumor antigens allow space for an optimistic view of the future.
    Vaccines 09/2015; 3(2):467-489. DOI:10.3390/vaccines3020467
  • OncoImmunology 08/2015; DOI:10.1080/2162402X.2015.1082705 · 6.27 Impact Factor
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    ABSTRACT: Continuous therapy (CT) prolongs progression-free survival 1 (PFS1; time from random assignment until the first progression or death), but chemotherapy-resistant relapse may negatively impact overall survival (OS). Progression-free survival 2 (PFS2; time from random assignment until the second progression or death) may represent an additional tool to estimate outcome. This study evaluates the benefit of novel agent-based CT versus fixed duration of therapy (FDT) in patients with newly diagnosed myeloma. We included patients enrolled onto three phase III trials that randomly assigned patients to novel agent-based CT versus FDT. Primary analyses were restricted to the intent-to-treat population eligible for CT (patients progression free and alive at 1 year after random assignment). Primary end points were PFS1, PFS2, and OS. All hazard ratios (HRs) and 95% CIs were adjusted for several potential confounders using Cox models. In the pooled analysis of the three trials, 604 patients were randomly assigned to CT and 614 were assigned to FDT. Median follow-up was 52 months. In the intent-to-treat CT population, CT (n = 417), compared with FDT (n = 410), significantly improved PFS1 (median, 32 v 16 months, respectively; HR, 0.47; 95% CI, 0.40 to 0.56; P < .001), PFS2 (median, 55 v 40 months, respectively; HR, 0.61; 95% CI, 0.50 to 0.75; P < .001), and OS (4-year OS, 69% v 60%, respectively; HR, 0.69; 95% CI, 0.54 to 0.88; P = .003). In this pooled analysis, CT significantly improved PFS1, PFS2, and OS. The improvement in PFS2 suggests that the benefit reported during first remission is not cancelled by a shorter second remission. PFS2 is a valuable end point to estimate long-term clinical benefit and should be included in future trials. © 2015 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 08/2015; DOI:10.1200/JCO.2014.60.2466 · 18.43 Impact Factor
  • Cancer Research 08/2015; 75(15 Supplement):3553-3553. DOI:10.1158/1538-7445.AM2015-3553 · 9.33 Impact Factor
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    ABSTRACT: The rat ErbB2 (rErbB2) protein is a 185-kDa glycoprotein belonging to the epidermal growth factor-related proteins (ErbB) of receptor tyrosine kinases. Overexpression and mutations of ErbB proteins lead to several malignancies including breast, lung, pancreatic, bladder and ovary carcinomas. ErbB2 is immunogenic and is an ideal candidate for cancer immunotherapy. We investigated the possibility of expressing the extracellular (EC) domain of rErbB2 (653 amino acids, aa) in Nicotiana benthamiana plants, testing the influence of the 23 aa transmembrane (TM) sequence on protein accumulation. Synthetic variants of the rErbB2 gene portion encoding the EC domain, optimized with a human codon usage and either linked to the full TM domain (rErbB2_TM, 676 aa), to a portion of it (rErbB2-pTM, 662 aa), or deprived of it (rErbB2_noTM, 653 aa) were cloned in the pEAQ-HT expression vector as 6X His tag fusions. All rErbB2 variants (72-74.5 kDa) were transiently expressed, but the TM was detrimental for rErbB2 EC accumulation. rERbB2_noTM was the most expressed protein; it was solubilized and purified with Nickel affinity resin. When crude soluble extracts expressing rErbB2_noTM were administered to BALB/c mice, specific rErbB2 immune responses were triggered. A potent antitumour activity was induced when vaccinated mice were challenged with syngeneic transplantable ErbB2(+) mammary carcinoma cells. To our knowledge, this is the first report of expression of rErbB2 in plants and of its efficacy in inducing a protective antitumour immune response, opening interesting perspectives for further immunological testing. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.
    Plant Biotechnology Journal 04/2015; DOI:10.1111/pbi.12367 · 5.75 Impact Factor
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    ABSTRACT: Whereas preclinical investigations and clinical studies have established that CD8(+) T cells can profoundly affect cancer progression, the underlying mechanisms are still elusive. Challenging the prevalent view that the beneficial effect of CD8(+) T cells in cancer is solely attributable to their cytotoxic activity, several reports have indicated that the ability of CD8(+) T cells to promote tumor regression is dependent on their cytokine secretion profile and their ability to self-renew. Evidence has also shown that the tumor microenvironment can disarm CD8(+) T cell immunity, leading to the emergence of dysfunctional CD8(+) T cells. The existence of different types of CD8(+) T cells in cancer calls for a more precise definition of the CD8(+) T cell immune phenotypes in cancer and the abandonment of the generic terms "pro-tumor" and "antitumor." Based on recent studies investigating the functions of CD8(+) T cells in cancer, we here propose some guidelines to precisely define the functional states of CD8(+) T cells in cancer.
    OncoImmunology 04/2015; 4(4):e998538. DOI:10.1080/2162402X.2014.998538 · 6.27 Impact Factor
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    ABSTRACT: The objective of this study was to compare a clustering approach to conventional analysis methods for assessing changes in pharmacokinetic parameters obtained from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) during antiangiogenic treatment in a breast cancer model. BALB/c mice bearing established transplantable her2+ tumors were treated with a DNA-based antiangiogenic vaccine or with an empty plasmid (untreated group). DCE-MRI was carried out by administering a dose of 0.05 mmol/kg of Gadocoletic acid trisodium salt, a Gd-based blood pool contrast agent (CA) at 1T. Changes in pharmacokinetic estimates (K(trans) and vp) in a nine-day interval were compared between treated and untreated groups on a voxel-by-voxel analysis. The tumor response to therapy was assessed by a clustering approach and compared with conventional summary statistics, with sub-regions analysis and with histogram analysis. Both the K(trans) and vp estimates, following blood-pool CA injection, showed marked and spatial heterogeneous changes with antiangiogenic treatment. Averaged values for the whole tumor region, as well as from the rim/core sub-regions analysis were unable to assess the antiangiogenic response. Histogram analysis resulted in significant changes only in the vp estimates (p<0.05). The proposed clustering approach depicted marked changes in both the K(trans) and vp estimates, with significant spatial heterogeneity in vp maps in response to treatment (p<0.05), provided that DCE-MRI data are properly clustered in three or four sub-regions. This study demonstrated the value of cluster analysis applied to pharmacokinetic DCE-MRI parametric maps for assessing tumor response to antiangiogenic therapy. Copyright © 2015. Published by Elsevier Inc.
    Magnetic Resonance Imaging 03/2015; 33(6). DOI:10.1016/j.mri.2015.03.005 · 2.09 Impact Factor
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    ABSTRACT: Recent studies reported complex post-transcriptional interplay among targets of a common pool of microRNAs, a class of small non-coding downregulators of gene expression. Behaving as microRNA-sponges, distinct RNA species may compete for binding to microRNAs and coregulate each other in a dose-dependent manner. Although previous studies in cell populations showed competition in vitro, the detailed dynamical aspects of this process, most importantly in physiological conditions, remains unclear. We address this point by monitoring protein expression of two targets of a common miRNA with quantitative single-cell measurements. In agreement with a detailed stochastic model of molecular titration, we observed that: (i) crosstalk between targets is possible only in particular stoichiometric conditions, (ii) a trade-off on the number of microRNA regulatory elements may induce the coexistence of two distinct cell populations, (iii) strong inter-targets correlations can be observed. This phenomenology is compatible with a small amount of mRNA target molecules per cell of the order of 10-100.
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    ABSTRACT: Perfluoropentane (PFP)-based oxygen-loaded nanobubbles (OLNBs) were previously proposed as adjuvant therapeutic tools for pathologies of different etiology sharing hypoxia as a common feature, including cancer, infection, and autoimmunity. Here we introduce a new platform of oxygen nanocarriers, based on 2H,3H-decafluoropentane (DFP) as core fluorocarbon. These new nanocarriers have been named oxygen-loaded nanodroplets (OLNDs) since DFP is liquid at body temperature, unlike gaseous PFP. Dextran-shelled OLNDs, available either in liquid or gel formulations, display spherical morphology, ~600 nm diameters, anionic charge, good oxygen carrying capacity, and no toxic effects on human keratinocytes after cell internalization. In vitro OLNDs result more effective in releasing oxygen to hypoxic environments than former OLNBs, as demonstrated by analysis through oxymetry. In vivo, OLNDs effectively enhance oxy-hemoglobin levels, as emerged from investigation by photoacoustic imaging. Interestingly, ultrasound (US) treatment further improves transdermal oxygen release from OLNDs. Taken together, these data suggest that US-activated, DFP-based OLNDs might be innovative, suitable and cost-effective devices to topically treat hypoxia-associated pathologies of the cutaneous tissues.
    PLoS ONE 03/2015; 10(3):e0119769. DOI:10.1371/journal.pone.0119769 · 3.23 Impact Factor
  • Francesca Gay · Federica Cavallo · Antonio Palumbo
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    ABSTRACT: Outcome of patients with multiple myeloma (MM) has greatly improved with the use of autologous stem cell transplantation (ASCT) and new agents, such as immunomodulatory drugs (thalidomide and lenalidomide) and proteasome inhibitors (bortezomib). When compared to conventional chemotherapy, high-dose melphalan with ASCT significantly improved response rates and progression-free survival, while overall survival benefit was not consistent across all trials. ASCT is considered the standard treatment for patients who are younger than 65 years and who do not have limiting comorbidities. New, effective agents have been introduced as part of induction, consolidation and maintenance treatments within ASCT and in combinations with chemotherapy for patients not eligible for ASCT. The remarkable results obtained with these regimens are questioning the role of ASCT for newly diagnosed MM patients. This article aims to delineate the role of ASCT in the era of novel agents based on the results of recent clinical trials.
    Drugs 03/2015; 75(4). DOI:10.1007/s40265-015-0367-0 · 4.34 Impact Factor
  • Emanuela Signori · Federica Cavallo
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    ABSTRACT: PIVAC-14, the Fourteenth Annual Conference on Progress in Vaccination Against Cancer (http://www.tati-group.de/pivac/), has been held on September 24-26, 2014, at the Donna Camilla Savelli Hotel in Rome. More than 110 attendees presented and discussed a plethora of new and promising results in a relaxed and informal atmosphere.The main topics covered by PIVAC-14 were cancer immunoprevention; the role of the tumor microenvironment in determining immunotherapy outcomes; the use of comparative oncology in predicting immunotherapy effectiveness; tumor escape mechanisms; and the latest experimental and clinical advances in various vaccination strategies, including peptide-, dendritic cell- and T cell-based vaccines. Special attention was paid to DNA vaccination and electrotransfer, which benefited from a dedicated section co-organized by COST Action TD1104-EP4Bio2Med, a European network of researchers working on the development of electroporation-based technologies and treatment in the fiel ...
    Cancer Immunology and Immunotherapy 03/2015; 64(10). DOI:10.1007/s00262-015-1676-6 · 3.94 Impact Factor
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    ABSTRACT: In this work the selective uptake of native horse spleen- ferritin and apoferritin loaded with MRI contrast agents have been assessed on human breast cancer cells (MCF-7, MDA-MB-231). The higher expression of L-ferritin receptors (SCARA5) let to an enhanced uptake in MCF-7 as shown in T2 and T1 weighted MR images, respectively. The high efficiency of ferritin internalization in MCF-7 has been exploited for the simultaneous delivery of curcumin, a natural therapeutic molecule endowed with antineoplastic and anti-inflammatory action, and the MRI contrast agent GdHPDO3A. This theranostic system is able to treat selectively breast cancer cells over-expressing ferritin receptors. By entrapping in apoferritin both Gd-HPDO3A and curcumin was possible to deliver a therapeutic dose of 97 μg/ml (as calculated by MRI) of this natural drug into MCF-7 cells, obtaining a significant reduction of cell proliferation.
    Nanoscale 03/2015; 7(15). DOI:10.1039/C5NR00352K · 7.39 Impact Factor
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    ABSTRACT: Maternal immunization is successfully applied against some life-threatening infectious diseases as it can protect the mother and her offspring through the passive transfer of maternal antibodies. Here, we sought to evaluate whether the concept of maternal immunization could also be applied to cancer immune-prevention. We have previously shown that antibodies induced by DNA vaccination against rat Her2 (neu) protect heterozygous neu-transgenic female (BALB-neuT) mice from autochthonous mammary tumor development. We, herein, seek to evaluate whether a similar maternal immunization can confer antitumor protection to BALB-neuT offspring. Significantly extended tumor-free survival was observed in BALB-neuT offspring born and fed by mothers vaccinated against neu, as compared to controls. Maternally derived anti-neu immunoglobulin G (IgG) was successfully transferred from mothers to newborns and was responsible for the protective effect. Vaccinated mothers and offspring also developed active immunity against neu as revealed by the presence of T-cell-mediated cytotoxicity against the neu immunodominant peptide. This active response was due to the milk transfer of immune complexes that were formed between the neu extracellular domain, shed from vaccine-transfected muscle cells, and the anti-neu IgG induced by the vaccine. These findings show that maternal immunization has the potential to hamper mammary cancer in genetically predestinated offspring and to develop into applications against lethal neonatal cancer diseases for which therapeutic options are currently unavailable.
    OncoImmunology 02/2015; 4(5):e1005500. DOI:10.1080/2162402X.2015.1005500 · 6.27 Impact Factor
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    ABSTRACT: Human cancer is so complex that in vivo preclinical models are needed if effective therapies are to be developed. Naturally occurring cancers in companion animals are therefore a great resource, as shown by the remarkable growth that comparative oncology has seen over the last 30 years. Cancer has become a leading cause of death in companion animals now that more pets are living long enough to develop the disease. Furthermore, more owners are seeking advanced and novel therapies for their pets as they are very much considered family members. Living in the same environments, pets and humans are often afflicted by the same types of cancer which show similar behavior and, in some species, express the same antigen molecules. The treatment of pet tumors using novel therapies is of compelling translational significance.
    Cancer Immunology and Immunotherapy 12/2014; 64(2). DOI:10.1007/s00262-014-1645-5 · 3.94 Impact Factor
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    ABSTRACT: During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches.
    Oncotarget 12/2014; 5(24). DOI:10.18632/oncotarget.2998 · 6.36 Impact Factor
  • Blood 12/2014; 124(21). · 10.45 Impact Factor
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    ABSTRACT: Unlabelled: A prominent feature of many human cancers is oncogene-driven activation of the DNA damage response (DDR) during early tumorigenesis. It has been shown previously that noninvasive imaging of the phosphorylated histone H2A variant H2AX, γH2AX, a DNA damage signaling protein, is possible using (111)In-labeled anti-γH2AX antibody conjugated to the cell-penetrating peptide transactivator of transcription (TAT). The purpose of this study was to investigate whether (111)In-anti-γH2AX-TAT detects the DDR during mammary oncogenesis in BALB-neuT mice. Methods: Mammary fat pads from BALB-neuT and wild-type mice (age, 40-106 d) were immunostained for γH2AX. (111)In-anti-γH2AX-TAT or a control probe was administered intravenously to BALB-neuT mice. SPECT was performed weekly and compared with tumor detection using palpation and dynamic contrast-enhanced MR imaging. Results: γH2AX expression was elevated in hyperplastic lesions in the mammary fat pads of BALB-neuT mice aged 76-106 d, compared with normal fat pads from younger mice and carcinomas from older mice (13.5 ± 1.2 γH2AX foci/cell vs. 5.2 ± 1.5 [P < 0.05] and 3.4 ± 1.1 [P < 0.001], respectively). Serial SPECT imaging revealed a 2.5-fold increase in (111)In-anti-γH2AX-TAT accumulation in the mammary fat pads of mice aged 76-106 d, compared with control probe (P = 0.01). The median time to detection of neoplastic lesions by (111)In-anti-γH2AX-TAT (defined as >5% injected dose per gram of tissue) was 96 d, compared with 120 and 131 d for dynamic contrast-enhanced MR imaging and palpation, respectively (P < 0.001). Conclusion: DDR imaging using (111)In-anti-γH2AX-TAT identified mammary tumors significantly earlier than MR imaging. Imaging the DDR holds promise for the detection of preneoplasia and as a technique for screening cancer-prone individuals.
    Journal of Nuclear Medicine 11/2014; DOI:10.2967/jnumed.114.142083 · 6.16 Impact Factor
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    ABSTRACT: The fact that cancer immunotherapy is considered to be a safe and successful weapon for use in combination with surgery, radiation, and chemotherapy treatments means that it has recently been chosen as Breakthrough of the Year 2013 by Science editors. Anticancer vaccines have been extensively tested, in this field, both in preclinical cancer models and in the clinic. However, tumor-associated antigens (TAAs) are often self-tolerated molecules and cancer patients suffer from strong immunosuppressive effects, meaning that the triggering of an effective anti-tumor immune response is difficult. One possible means to overcome immunological tolerance to self-TAAs is of course the use of vaccines that code for xenogeneic proteins. However, a low-affinity antibody response against the self-homologous protein expressed by cancer cells is generally induced by xenovaccination. This issue becomes extremely limiting when working with tumors in which the contribution of the humoral rather than the cellular immune response is required if tumor growth is to be hampered. A possible way to avoid this problem is to use hybrid vaccines which code for chimeric proteins that include both homologous and xenogeneic moieties. In fact, a superior protective anti-tumor immune response against ErbB2(+) transplantable and autochthonous mammary tumors was observed over plasmids that coded for the fully rat or fully human proteins when hybrid plasmids that coded for chimeric rat/human ErbB2 protein were tested in ErbB2 transgenic mice. In principle, these findings may become the basis for a new rational means of designing effective vaccines against TAAs.
    Current topics in microbiology and immunology 10/2014; DOI:10.1007/82_2014_426 · 4.10 Impact Factor

Publication Stats

6k Citations
1,314.70 Total Impact Points


  • 1992–2015
    • Università degli Studi di Torino
      • • Center for Experimental Research and Medical Studies
      • • Molecular Biotechnology Center
      • • Department of Medical Science
      • • Dipartimento di Scienze Cliniche e Biologiche
      Torino, Piedmont, Italy
  • 2012–2013
    • Azienda Ospedaliera Città della Salute e della Scienza di Torino
      • Division of Hematology
      Torino, Piedmont, Italy
  • 2011
    • University of Camerino
      Camerino, The Marches, Italy
  • 2010
    • University of Rome Tor Vergata
      Roma, Latium, Italy
  • 2007–2009
    • Ospedale San Giovanni Battista, ACISMOM
      Torino, Piedmont, Italy
  • 2005
    • Wayne State University
      Detroit, Michigan, United States
  • 1996–2005
    • University of Bologna
      • Department of Experimental, Diagnostic and Specialty Medicine DIMES
      Bolonia, Emilia-Romagna, Italy
  • 1999
    • National Research Council
      Oristany, Sardinia, Italy
  • 1997
    • Istituto Nazionale Tumori "Fondazione Pascale"
      Napoli, Campania, Italy
  • 1994
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      • Center for Aging Sciences CESI
      Chieta, Abruzzo, Italy