Research Topics
Genomes and Genes | Luca GattinoniSummaryAffiliation: National Institutes of Health Country: USA Publications
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Publications
Extrathymic generation of tumor-specific T cells from genetically engineered human hematopoietic stem cells via Notch signalingYangbing Zhao
Surgery Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 1201, USA
Cancer Res 67:2425-9. 2007..The genetic manipulation of HSCs has broad implications for ACT of cancer...
Effective tumor treatment targeting a melanoma/melanocyte-associated antigen triggers severe ocular autoimmunityDouglas C Palmer
National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 105:8061-6. 2008..These findings have particular importance for immunotherapies directed against self-antigens and highlight the need for targeting unique tumor antigens not expressed in critical tissues...
Paths to stemness: building the ultimate antitumour T cellLuca Gattinoni
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Nat Rev Cancer 12:671-84. 2012..Conferring stemness to antitumour T cells might unleash the full potential of cellular therapies...
Adoptive immunotherapy for cancer: building on successLuca Gattinoni
National Cancer Institute, National Institutes of Health, Mark O Hatfield Clinical Research Center, Room 3 5762, 10 Center Drive, Bethesda, Maryland 20892 1201, USA
Nat Rev Immunol 6:383-93. 2006....
Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cellsLuca Gattinoni
Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA
Nat Med 15:808-13. 2009..These findings reveal a key role for Wnt signaling in the maintenance of 'stemness' in mature memory CD8(+) T cells and have major implications for the design of new vaccination strategies and adoptive immunotherapies...
A human memory T cell subset with stem cell-like propertiesLuca Gattinoni
Center for Cancer Research, National Cancer Institute, US National Institutes of Health NIH, Bethesda, Maryland, USA
Nat Med 17:1290-7. 2011..The identification of a human stem cell-like memory T cell population is of direct relevance to the design of vaccines and T cell therapies...
Increased intensity lymphodepletion enhances tumor treatment efficacy of adoptively transferred tumor-specific T cellsClaudia Wrzesinski
Surgery Branch, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA
J Immunother 33:1-7. 2010..Thus, increased intensity lymphodepletion triggers enhanced tumor treatment efficacy and the benefits of high-dose total body irradiation must be titrated against its risks...
Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signalingChrystal M Paulos
National Cancer Institute NCI, NIH, Bethesda, Maryland 20892 1502, USA
J Clin Invest 117:2197-204. 2007..Thus, disruption of the homeostatic balance between the host and microbes can enhance cell-based tumor immunotherapy...
Hematopoietic stem cells promote the expansion and function of adoptively transferred antitumor CD8 T cellsClaudia Wrzesinski
National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
J Clin Invest 117:492-501. 2007..These findings indicate that CD8(+) T cell-mediated tumor responses can be efficiently driven by HSCs in the myeloablative setting and have substantial implications for the design of new antitumor immunotherapies...
IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapyChristian S Hinrichs
National Cancer Institute, Surgery Branch, National Institutes of Health, Bethesda, MD 20892 1502, USA
Blood 111:5326-33. 2008..Thus, the efficacy of CD8(+) T cells for adoptive immunotherapy can be influenced by opposing differentiation programs conferred by IL-2 and IL-21, a finding with important implications for the development of cellular cancer therapies...
Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunityChristian S Hinrichs
National Cancer Institute, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 106:17469-74. 2009..These results indicate that insertion of genes that confer antitumor specificity into naïve rather than central memory CD8(+) T cells may allow superior efficacy upon adoptive transfer...
Adoptive transfer of allogeneic tumor-specific T cells mediates effective regression of large tumors across major histocompatibility barriersAndrea Boni
Clinical Research Center, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Blood 112:4746-54. 2008..Taken together, these data indicate that the use of tumor-specific allogeneic CD8(+) T cells or CD4(+) can result in significant antitumor effects in the absence of measurable GVHD...
Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cellsChristopher A Klebanoff
Howard Hughes Medical Institute, National Institutes of Health Research Scholars Program, Bethesda, MD 20814, USA
Proc Natl Acad Sci U S A 102:9571-6. 2005..Thus, tumor-reactive CD8+ T cell populations with the phenotypic and functional attributes of T(CM) may be superior to T(EM)/effector T cells for adoptive immunotherapies using concomitant tumor-antigen vaccination...
Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cellsLuca Gattinoni
Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1502, USA
J Clin Invest 115:1616-26. 2005..These findings suggest that the current methodology for selecting T cells for transfer is inadequate and provide new criteria for the generation and the screening of optimal lymphocyte populations for adoptive immunotherapy...
Th17 cells are long lived and retain a stem cell-like molecular signaturePawel Muranski
National Cancer Institute, Bethesda, MD 20892, USA
Immunity 35:972-85. 2011..Thus, Th17 cells are not always short lived and are a less-differentiated subset capable of superior persistence and functionality...
Determinants of successful CD8+ T-cell adoptive immunotherapy for large established tumors in miceChristopher A Klebanoff
Center for Cancer Research CCR, National Cancer Institute NCI, NIH, Bethesda, Maryland 20892, USA
Clin Cancer Res 17:5343-52. 2011..However, the relative contributions of each these individual components to the magnitude of the antitumor response have yet to be quantified...
Human effector CD8+ T cells derived from naive rather than memory subsets possess superior traits for adoptive immunotherapyChristian S Hinrichs
National Cancer Institute, Bethesda, MD, USA
Blood 117:808-14. 2011..Thus, these data suggest that naive cells resist terminal differentiation, or "exhaustion," maintain high replicative potential, and therefore may be the superior subset for use in adoptive immunotherapy...
T-cell receptor gene therapy of established tumors in a murine melanoma modelJohn D Abad
Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Immunother 31:1-6. 2008..This model may be a powerful tool for evaluating future TCR gene transfer-based strategies...
Toll-like receptors in tumor immunotherapyChrystal M Paulos
National Cancer Institute, NIH, Mark O Hatfield Clinical Research Center, Bethesda, Maryland 20892 1502, USA
Clin Cancer Res 13:5280-9. 2007..We also discuss alternate regimens to chemotherapy or TBI, which might be used to safely treat patients with advanced disease and promote tumor regression...
Tumor-specific Th17-polarized cells eradicate large established melanomaPawel Muranski
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Mark O Hatfield Clinical Research Center, Bethesda, MD 20892, USA
Blood 112:362-73. 2008..This principle should be considered in designing clinical trials involving adoptive transfer-based immunotherapy of human malignancies...
Vaccine-stimulated, adoptively transferred CD8+ T cells traffic indiscriminately and ubiquitously while mediating specific tumor destructionDouglas C Palmer
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 173:7209-16. 2004..The ability to induce ubiquitous homing and specific tumor destruction may be important in the case of noninflammatory metastatic tumor foci...
Tumor-specific CD8+ T cells expressing interleukin-12 eradicate established cancers in lymphodepleted hostsSid P Kerkar
Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA
Cancer Res 70:6725-34. 2010..Our findings reveal an approach to genetically modify T cells to reduce the cell number needed, eliminate the need for vaccines or systemic IL-2, and improve immunotherapy efficacy based on adoptive transfer of gene-engineered T cells...
Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cellsYun Ji
Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA
Nat Immunol 12:1230-7. 2011..Our findings identify the Blimp-1-Id3-E2A axis as a key molecular switch that determines whether effector CD8(+) T cells are programmed to die or enter the memory pool...
Programming tumor-reactive effector memory CD8+ T cells in vitro obviates the requirement for in vivo vaccinationChristopher A Klebanoff
Howard Hughes Medical Institute National Institutes of Health Research Scholars Program, Bethesda, MD, USA
Blood 114:1776-83. 2009..These findings extend the phenomenon of a programmable effector response to memory CD8(+) T cells and have major implications for the design of current adoptive-cell transfer trials...
CTLA-4 dysregulation of self/tumor-reactive CD8+ T-cell function is CD4+ T-cell dependentLuca Gattinoni
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Mark O Hatfield Clinical Research Center, 10 Center Drive, Room 3 5750, Bethesda, MD 20892, USA
Blood 108:3818-23. 2006..These results indicated that CD8(+) CLTA-4(-/-) T-cell-mediated autoimmunity and tumor immunity required CD4(+) T cells in which the function was dysregulated by the absence of CTLA-4-mediated negative costimulation...
Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cellsLuca Gattinoni
Center for Cancer Research, National Cancer Institute (NCI, National Institutes of Health (NIH, Bethesda, MD 20892, USA
J Exp Med 202:907-12. 2005..Thus, the restricted availability of homeostatic cytokines can be a contributing factor to peripheral tolerance, as well as a limiting resource for the effectiveness of tumor-specific T cells...
In vitro generated anti-tumor T lymphocytes exhibit distinct subsets mimicking in vivo antigen-experienced cellsShicheng Yang
Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
Cancer Immunol Immunother 60:739-49. 2011....
Genetic engineering of murine CD8+ and CD4+ T cells for preclinical adoptive immunotherapy studiesSid P Kerkar
Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Immunother 34:343-52. 2011..These results indicate that preclinical murine models of adoptive immunotherapies are more practical using γ-retroviral rather than lentiviral vectors...
Bedside to bench and back again: how animal models are guiding the development of new immunotherapies for cancerSteven E Finkelstein
National Cancer Institute, National Institutes of Health, Building 10, Room 2B 46, 10 Center Drive, Bethesda, MD 20892, USA
J Leukoc Biol 76:333-7. 2004..Complete responders frequently develop autoimmunity with vitiligo at the former tumor site that often spreads to involve the whole coat. These findings have important implications for the design of immunotherapy trials in humans...
High-efficiency transfection of primary human and mouse T lymphocytes using RNA electroporationYangbing Zhao
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Mol Ther 13:151-9. 2006..The results of this study indicate that mRNA electroporation provides a powerful tool to introduce genes into both human and murine primary T lymphocytes...
CD8+ T-cell memory in tumor immunology and immunotherapyChristopher A Klebanoff
Howard Hughes Medical Institute-National Institutes of Health (NIH) Research Scholars Program, Bethesda, MD 20892-1502, USA
Immunol Rev 211:214-24. 2006..Therapeutic vaccines for cancer and chronic infectious diseases may achieve consistent efficacy by ablation of the dysfunctional immune state and the provision of newly generated, non-corrupted memory cells by adoptive cell transfer...
Pharmacologic induction of CD8+ T cell memory: better living through chemistryLuca Gattinoni
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Sci Transl Med 1:11ps12. 2009..These findings raise the exciting new possibility of using small molecules, many of which are already approved for human use, for the pharmacologic induction of immunologic memory...
Programming CD8+ T cells for effective immunotherapyChristian S Hinrichs
National Cancer Institute, Surgery Branch, National Institutes of Health, Bethesda, MD 20892, USA
Curr Opin Immunol 18:363-70. 2006..The epigenetic mechanisms by which T cells are programmed are just beginning to be elucidated. Understanding the mechanisms that control CD8+ T-cell differentiation is important in the development of novel immunotherapy strategies...
Sorting through subsets: which T-cell populations mediate highly effective adoptive immunotherapy?Christopher A Klebanoff
Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA
J Immunother 35:651-60. 2012....
Wnt/beta-catenin signaling in T-cell immunity and cancer immunotherapyLuca Gattinoni
Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
Clin Cancer Res 16:4695-701. 2010....
IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cellsChristopher A Klebanoff
Howard Hughes Medical Institute National Institutes of Health Research Scholars Program, Bethesda, MD 20814, USA
Proc Natl Acad Sci U S A 101:1969-74. 2004..These results provide several avenues for improving adoptive immunotherapy of cancer in patients...
Regulation of nucleosome landscape and transcription factor targeting at tissue-specific enhancers by BRG1Gangqing Hu
Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Genome Res 21:1650-8. 2011..Intriguingly, we find that the nucleosome shifting specifically facilitates binding of TAL1 but not GATA1 and is linked to subsequent transcriptional regulation of target genes...
Identification, isolation and in vitro expansion of human and nonhuman primate T stem cell memory cellsEnrico Lugli
Immunotechnology Section, Vaccine Research Center VRC, National Institute of Allergy and Infectious Diseases, US National Institutes of Health NIH, Bethesda, MD, USA
Nat Protoc 8:33-42. 2013..We also indicate multiple strategies for their efficient expansion in vitro at consistent numbers for functional characterization or adoptive transfer experiments...
New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancerDavid F Stroncek
Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, USA
J Transl Med 10:48. 2012..In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies...
CD8(+) T lymphocytes isolated from renal cancer patients recognize tumour cells through an HLA- and TCR/CD3-independent pathwayIlaria Lionello
Cancer Immunotherapy and Gene Therapy Program, Scientific Institute H San Raffaele, Milan, Italy
Cancer Immunol Immunother 56:1065-76. 2007..The aim of this study was to characterize the immune response of patients affected by renal cell carcinoma (RCC)...
Unusual aspects of melanoma. Case 2. Regionally advanced nasal cavity melanomaMichele Del Vecchio
Department of Medical Oncology, Istituto Nazionale dei Tumori of Milan, Italy
J Clin Oncol 22:745-6. 2004
Prognostic significance of cancer-testis gene expression in resected non-small cell lung cancer patientsGiulio Melloni
Department of Thoracic Surgery, Scientific Institute H. San Raffaele, Italy
Oncol Rep 12:145-51. 2004..In conclusion, the detection of GAGE gene expression by RT-PCR appears to be an independent survival predictor in completely resected NSCLC patients...
Renal cancer treatment: a review of the literatureLuca Gattinoni
Operative Unit of Medical Oncology B, National Cancer Institute, Milan, Italy
Tumori 89:476-84. 2003..New approaches such as monoclonal antibodies, vaccines, gene therapy, angiogenesis inhibitors and allogeneic cell transplantation and their possible clinical applications are also discussed...
Could exemestane affect insulin-like growth factors, interleukin 6 and bone metabolism in postmenopausal advanced breast cancer patients after failure on aminoglutethimide, anastrozole or letrozole?Leonardo Ferrari
Nuclear Medicine Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, I 20133 Milano, Italy
Int J Oncol 22:1081-9. 2003..The observed variations seem to be mainly linked to the circulating oestrogen levels rather than directly to the way of action of the AI employed...
