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MacLean Hall, Hao Liu, Mokenge Malafa, Barbara Centeno, Pamela J Hodul, José Pimiento, Shari Pilon-Thomas, Amod A Sarnaik
BACKGROUND: We evaluated whether tumor infiltrating lymphocytes (TIL) could be expanded from surgically resected tumors from pancreatic cancer patients. METHODS: Tumors were resected from pancreatic cancer patients. Tumors were minced into fragments and cultured in media containing high dose interleukin-2 (IL-2) for up to 6 weeks. T cell phenotype, activation markers, and reactivity were measured. RESULTS: TIL expansion was measured in 19 patient samples...
2016: Journal for Immunotherapy of Cancer
Wolfgang Merkt, Hanns-Martin Lorenz, Carsten Watzl
BACKGROUND: Rituximab has broad and increasing application in rheumatic diseases. It is known from lymphoma studies that natural killer (NK) cells can lyse rituximab-coated transformed B cells. However, the role of NK cells in mediating rituximab-induced depletion of non-malignant B cells is unknown. The purpose of this study was to provide fundamental data on rituximab-mediated effects on NK cells in PBMCs without tumor cells, in order to simulate effects that could be relevant in patients with rheumatic disease...
2016: Arthritis Research & Therapy
Wolfgang Merkt, Maren Claus, Norbert Blank, Michael Hundemer, Adelheid Cerwenka, Hanns-Martin Lorenz, Carsten Watzl
BACKGROUND: The role of natural killer (NK) cells in granulomatosis with polyangiitis (GPA) is poorly understood. We recently reported that peripheral blood NK cell percentages correlate with the suppression of GPA activity (cohort I). The purpose of the current study was to further characterize NK cell subsets, phenotype and function in a second GPA cohort (cohort II). METHODS: Peripheral blood lymphocyte subsets were analyzed at a clinical diagnostic laboratory...
2016: Arthritis Research & Therapy
Hans Hammers
PURPOSE OF REVIEW: Kidney cancer, in particular clear cell renal cell carcinoma (ccRCC) has long been considered to be sensitive to immunotherapies. With the recent breakthroughs in immunotherapy for solid tumors and the recent approval of the first immune checkpoint inhibitor for ccRCC, we are reviewing the history of immunotherapy in kidney cancer, describing its current state and look into the future of a rapidly evolving landscape in immunotherapy for kidney cancer. RECENT FINDINGS: Systemic treatment options over the past decade have been dominated by targeted therapies inhibiting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways...
November 2016: Current Opinion in Urology
Wei Wang, Amy K Erbe, Kory A Alderson, Emily Phillips, Mikayla Gallenberger, Jacek Gan, Dario Campana, Jacquelyn A Hank, Paul M Sondel
Infusion of allogeneic NK cells is a potential immunotherapy for both hematopoietic malignancies and solid tumors. Interactions between killer immunoglobulin-like receptors (KIR) on human NK cells and KIR-ligands on tumor cells influence the magnitude of NK function. To obtain sufficient numbers of activated NK cells for infusion, one potent method uses cells from the K562 human erythroleukemia line that have been transfected to express activating 41BB ligand (41BBL) and membrane-bound interleukin 15 (mbIL15)...
September 2016: Cancer Immunology, Immunotherapy: CII
Marie T Kim, Martin J Richer, Brett P Gross, Lyse A Norian, Vladimir P Badovinac, John T Harty
U.S. Food and Drug Administration-approved high-dose IL-2 therapy and dendritic cell (DC) immunization offer time-tested treatments for malignancy, but with defined issues of short in vivo t1/2, toxicity, and modest clinical benefit. Complexes of IL-2 with specific mAbs (IL-2c) exhibit improved stability in vivo with reduced toxicity and are capable of stimulating NK cell and memory phenotype CD8 T cell proliferation. In this study, we demonstrate that IL-2c treatment in tumor-bearing mice can enhance NK cell and tumor-specific CD8 T cell numbers...
November 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Susann Szmania, Natalia Lapteva, Tarun Garg, Amy Greenway, Joshuah Lingo, Bijay Nair, Katie Stone, Emily Woods, Junaid Khan, Justin Stivers, Susan Panozzo, Dario Campana, William T Bellamy, Molly Robbins, Joshua Epstein, Shmuel Yaccoby, Sarah Waheed, Adrian Gee, Michele Cottler-Fox, Cliona Rooney, Bart Barlogie, Frits van Rhee
Highly activated/expanded natural killer (NK) cells can be generated by stimulation with the human leukocyte antigen-deficient cell line K562, genetically modified to express 41BB-ligand and membrane-bound interleukin (IL)15. We tested the safety, persistence, and activity of expanded NK cells generated from myeloma patients (auto-NK) or haploidentical family donors (allo-NK) in heavily pretreated patients with high-risk relapsing myeloma. The preparative regimen comprised bortezomib only or bortezomib and immunosuppression with cyclophosphamide, dexamethasone, and fludarabine...
January 2015: Journal of Immunotherapy
Daniel Abate-Daga, Kiran H Lagisetty, Eric Tran, Zhili Zheng, Luca Gattinoni, Zhiya Yu, William R Burns, Anne M Miermont, Yaroslav Teper, Udo Rudloff, Nicholas P Restifo, Steven A Feldman, Steven A Rosenberg, Richard A Morgan
Despite advances in the understanding of its molecular pathophysiology, pancreatic cancer remains largely incurable, highlighting the need for novel therapies. We developed a chimeric antigen receptor (CAR) specific for prostate stem cell antigen (PSCA), a glycoprotein that is overexpressed in pancreatic cancer starting at early stages of malignant transformation. To optimize the CAR design, we used antigen-recognition domains derived from mouse or human antibodies, and intracellular signaling domains containing one or two T cell costimulatory elements, in addition to CD3zeta...
December 2014: Human Gene Therapy
Sujin Lee, Robert S Mittler, Martin L Moore
Respiratory syncytial virus (RSV) causes significant morbidity and mortality in children and the elderly. No vaccines for RSV are in use. Because of immunosenescence, the immunologic requirements for a successful RSV vaccine in the elderly might differ from a RSV vaccine for young children. Using an aged mouse model of RSV pathogenesis, we found that aged mice had impaired Ag-specific CD8(+) T cell responses and delayed RSV clearance compared with young mice. To study vaccine-elicited RSV-specific CD8(+) T cells in aged mice, we used a peptide vaccine approach...
January 1, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Andreas A Hombach, Hinrich Abken
No abstract text is available yet for this article.
July 2013: Immunotherapy
Álvaro Teijeira, Asís Palazón, Saray Garasa, Diego Marré, Cristina Aubá, Anne Rogel, Ohiana Murillo, Iván Martínez-Forero, François Lang, Ignacio Melero, Ana Rouzaut
CD137/TNFR9/41BB was originally described as a surface molecule present on activated T and NK cells. However, its expression is broader among leukocytes, and it is also detected on hypoxic endothelial cells and inflamed blood vessels, as well as in atherosclerotic lesions. Here, we demonstrate that lymphatic endothelial cells (LECs) up-regulate CD137 expression from undetectable baseline levels on stimulation with TNF-α, LPS, and IL-1β. CD137 cross-linking with an agonistic mAb results in NF-κB nuclear translocation, followed by up-regulation of VCAM and a 3-fold increase in the production of the chemokine CCL21...
August 2012: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
John Stagg, Sherene Loi, Upulie Divisekera, Shin Foong Ngiow, Helene Duret, Hideo Yagita, Michele W Teng, Mark J Smyth
Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor-2 (HER2/ErbB-2), has become the mainstay of treatment for HER2-positive breast cancer. Nevertheless, its exact mechanism of action has not been fully elucidated. Although several studies suggest that Fc receptor-expressing immune cells are involved in trastuzumab therapy, the relative contribution of lymphocyte-mediated cellular cytotoxicity and antitumor cytokines remains unknown. We report here that anti-ErbB-2 mAb therapy is dependent on the release of type I and type II IFNs but is independent of perforin or FasL...
April 26, 2011: Proceedings of the National Academy of Sciences of the United States of America
Hiroyuki Fujisaki, Harumi Kakuda, Noriko Shimasaki, Chihaya Imai, Jing Ma, Timothy Lockey, Paul Eldridge, Wing H Leung, Dario Campana
Infusions of natural killer (NK) cells are an emerging tool for cancer immunotherapy. The development of clinically applicable methods to produce large numbers of fully functional NK cells is a critical step to maximize the potential of this approach. We determined the capacity of the leukemia cell line K562 modified to express a membrane-bound form of interleukin (IL)-15 and 41BB ligand (K562-mb15-41BBL) to generate human NK cells with enhanced cytotoxicity. Seven-day coculture with irradiated K562-mb15-41BBL induced a median 21...
May 1, 2009: Cancer Research
Karen A Herd, Carsten Wiethe, Robert W Tindle
T cell mediated immune responses are induced following interaction of MHC-presented epitope on professional antigen presenting cells such as dendritic cells (DCs) with cognate T cell receptor. Up-regulation of receptor-ligand pairs of costimulatory molecules linking DC to T cell enhances the resulting T cell responses. This 'second signalling' occurs through the B7 molecules CD80/86 expressed by DCs, and importantly through members of the TNF ligand/TNF receptor superfamilies. We have previously shown that co-expression of RANK/RANKL or 41BB-L in addition to tumour antigen in dendritic cells augmented cognate effector and memory tumour antigen-directed cytotoxic T cell responses when the DCs were used to immunise mice...
July 9, 2007: Vaccine
A Bauer, L Savelyeva, A Claas, C Praml, F Berthold, M Schwab
In human neuroblastomas, the distal portion of 1p is frequently deleted, as if one or more tumor suppressor genes from this region were involved in neuroblastoma tumorigenesis. Earlier studies had identified a smallest region of overlapping deletion (SRO) spanning approximately 23 cM between the most distally retained D1S80 and by the proximally retained D1S244. In pursuit of generating a refined delineation of the minimally deleted region, we have analyzed 49 neuroblastomas of different stages for loss of heterozygosity (LOH) from 1pter to 1p35 by employing 26 simple sequence length polymorphisms...
July 2001: Genes, Chromosomes & Cancer
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