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Cliona rooney

Carlos A Ramos, Barbara Savoldo, Vicky Torrano, Brandon Ballard, Huimin Zhang, Olga Dakhova, Enli Liu, George Carrum, Rammurti T Kamble, Adrian P Gee, Zhuyong Mei, Meng-Fen Wu, Hao Liu, Bambi Grilley, Cliona M Rooney, Malcolm K Brenner, Helen E Heslop, Gianpietro Dotti
BACKGROUND: Treatment of B cell malignancies with adoptive transfer of T cells with a CD19-specific chimeric antigen receptor (CAR) shows remarkable clinical efficacy. However, long-term persistence of T cells targeting CD19, a pan-B cell marker, also depletes normal B cells and causes severe hypogammaglobulinemia. Here, we developed a strategy to target B cell malignancies more selectively by taking advantage of B cell light Ig chain restriction. We generated a CAR that is specific for the κ light chain (κ...
July 1, 2016: Journal of Clinical Investigation
Natalia Lapteva, Robin Parihar, Lisa A Rollins, Adrian P Gee, Cliona M Rooney
Recent advances in methods for the ex vivo expansion of human natural killer (NK) cells have facilitated the use of these powerful immune cells in clinical protocols. Further, the ability to genetically modify primary human NK cells following rapid expansion allows targeting and enhancement of their immune function. We have successfully adapted an expansion method for primary NK cells from peripheral blood mononuclear cells or from apheresis products in gas permeable rapid expansion devices (G-Rexes). Here, we describe an optimized protocol for rapid and robust NK cell expansion as well as a method for highly efficient retroviral transduction of these ex vivo expanded cells...
2016: Methods in Molecular Biology
Swati Naik, Sarah K Nicholas, Caridad A Martinez, Ann M Leen, Patrick J Hanley, Steven M Gottschalk, Cliona M Rooney, I Celine Hanson, Robert A Krance, Elizabeth J Shpall, Conrad R Cruz, Persis Amrolia, Giovanna Lucchini, Nancy Bunin, Jennifer Heimall, Orly R Klein, Andrew R Gennery, Mary A Slatter, Mark A Vickers, Jordan S Orange, Helen E Heslop, Catherine M Bollard, Michael D Keller
BACKGROUND: Viral infections are a leading fatal complication for patients with primary immunodeficiencies (PIDs) who require hematopoietic stem cell transplantation (HSCT). Use of virus-specific T lymphocytes (VSTs) has been successful for the treatment and prevention of viral infections after HSCT for malignant and nonmalignant conditions. Here we describe the clinical use of VSTs in patients with PIDs at 4 centers. OBJECTIVE: We sought to evaluate the safety and efficacy of VSTs for treatment of viral infections in patients with PIDs...
May 2016: Journal of Allergy and Clinical Immunology
Daniel L Galvan, Richard T O'Neil, Aaron E Foster, Leslie Huye, Adham Bear, Cliona M Rooney, Matthew H Wilson
Adoptive transfer of gene modified T cells provides possible immunotherapy for patients with cancers refractory to other treatments. We have previously used the non-viral piggyBac transposon system to gene modify human T cells for potential immunotherapy. However, these previous studies utilized adoptive transfer of modified human T cells to target cancer xenografts in highly immunodeficient (NOD-SCID) mice that do not recapitulate an intact immune system. Currently, only viral vectors have shown efficacy in permanently gene-modifying mouse T cells for immunotherapy applications...
2015: PloS One
Stephen Gottschalk, Cliona M Rooney
Epstein-Barr virus (EBV) is associated with a range of malignancies involving B cells, T cells, natural killer (NK) cells, epithelial cells, and smooth muscle. All of these are associated with the latent life cycles of EBV, but the pattern of latency-associated viral antigens expressed in tumor cells depends on the type of tumor. EBV-specific T cells (EBVSTs) have been explored as prophylaxis and therapy for EBV-associated malignancies for more than two decades. EBVSTs have been most successful as prophylaxis and therapy for post-transplant lymphoproliferative disease (PTLD) , which expresses the full array of latent EBV antigens (type 3 latency), in hematopoietic stem-cell transplant (HSCT) recipients...
2015: Current Topics in Microbiology and Immunology
Teresa Manzo, Helen E Heslop, Cliona M Rooney
Adoptively transferred antigen-specific T cells that recognize tumor antigens through their native receptors have many potential benefits as treatment for virus-associated diseases and malignancies, due to their ability to selectively recognize tumor antigens, expand and persist to provide long-term protection. Infusions of T cells targeting Epstein-Barr virus (EBV) antigens have shown encouraging response rates in patients with post-transplant lymphoproliferative disease as well as EBV-positive lymphomas and nasopharyngeal cancer, although a recent study also showed that human papilloma virus-reactive T cells can induce complete regression of metastatic cervical cancer...
October 15, 2015: Human Molecular Genetics
Xiaoou Zhou, Gianpietro Dotti, Robert A Krance, Caridad A Martinez, Swati Naik, Rammurti T Kamble, April G Durett, Olga Dakhova, Barbara Savoldo, Antonio Di Stasi, David M Spencer, Yu-Feng Lin, Hao Liu, Bambi J Grilley, Adrian P Gee, Cliona M Rooney, Helen E Heslop, Malcolm K Brenner
To test the feasibility of a single T-cell manipulation to eliminate alloreactivity while sparing antiviral and antitumor T cells, we infused 12 haploidentical hematopoietic stem cell transplant patients with increasing numbers of alloreplete haploidentical T cells expressing the inducible caspase 9 suicide gene (iC9-T cells). We determined whether the iC9-T cells produced immune reconstitution and if any resultant graft-versus-host disease (GVHD) could be controlled by administration of a chemical inducer of dimerization (CID; AP1903/Rimiducid)...
June 25, 2015: Blood
Soranobu Ninomiya, Neeharika Narala, Leslie Huye, Shigeki Yagyu, Barbara Savoldo, Gianpietro Dotti, Helen E Heslop, Malcolm K Brenner, Cliona M Rooney, Carlos A Ramos
Although T cells expressing CD19-specific chimeric antigen receptors (CARs) are a promising new therapy for B-cell malignancies, objective responses are observed at lower frequencies in patients with lymphoma than in those with acute B-cell leukemia. We postulated that the tumor microenvironment suppresses CAR-expressing T cells (CARTs) through the activity of indoleamine 2,3-dioxygenase (IDO), an intracellular enzyme that converts tryptophan into metabolites that inhibit T -: cell activity. To investigate the effects of tumor IDO on CD19-CART therapy, we used a xenograft lymphoma model expressing IDO as a transgene...
June 18, 2015: Blood
Karim Hadjri, Cliona Rooney, Verity Faith
This article reviews the current state of housing for people with dementia by exploring housing choices available to this group, and identifying potential issues with design of care homes. Older people who wish to age in place are faced with the challenge of adapting their domestic environment to ensure independence, accessibility, and social connectivity. This is even more challenging for people with dementia who continue to live at home, given the risks of self-harm and getting lost. More imaginative and inclusive forms of collective housing are needed...
2015: HERD
Patrick J Hanley, Jan J Melenhorst, Sarah Nikiforow, Phillip Scheinberg, James W Blaney, Gail Demmler-Harrison, C Russell Cruz, Sharon Lam, Robert A Krance, Kathryn S Leung, Caridad A Martinez, Hao Liu, Daniel C Douek, Helen E Heslop, Cliona M Rooney, Elizabeth J Shpall, A John Barrett, John R Rodgers, Catherine M Bollard
Adoptive transfer of cytomegalovirus (CMV)-specific T cells derived from adult seropositive donors can effectively restore antiviral immunity after transplantation. However, CMV-seronegative donors lack CMV-specific memory T cells, which restricts the availability of virus-specific T cells for immunoprophylaxis. We demonstrate the feasibility of deriving CMV-specific T cells from naïve cells for T cell therapy. Naïve T cells primed to recognize CMV were restricted to different, atypical epitopes than T cells derived from CMV-seropositive individuals; however, these two cell populations had similar avidities...
April 29, 2015: Science Translational Medicine
Michael Schmueck-Henneresse, Radwa Sharaf, Katrin Vogt, Benjamin J D Weist, Sybille Landwehr-Kenzel, Henrike Fuehrer, Anke Jurisch, Nina Babel, Cliona M Rooney, Petra Reinke, Hans-Dieter Volk
Memory T cells expressing stem cell-like properties have been described recently. The capacity of self-renewal and differentiation into various memory/effector subsets make them attractive for adoptive T cell therapy to combat severe virus infections and tumors. The very few reports on human memory stem T cells (T(SCM)) are restricted to analyses on polyclonal T cells, but extensive data on Ag-specific T(SCM )are missing. This might be due to their very low frequency limiting their enrichment and characterization...
June 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Nabil Ahmed, Vita S Brawley, Meenakshi Hegde, Catherine Robertson, Alexia Ghazi, Claudia Gerken, Enli Liu, Olga Dakhova, Aidin Ashoori, Amanda Corder, Tara Gray, Meng-Fen Wu, Hao Liu, John Hicks, Nino Rainusso, Gianpietro Dotti, Zhuyong Mei, Bambi Grilley, Adrian Gee, Cliona M Rooney, Malcolm K Brenner, Helen E Heslop, Winfried S Wels, Lisa L Wang, Peter Anderson, Stephen Gottschalk
PURPOSE: The outcome for patients with metastatic or recurrent sarcoma remains poor. Adoptive therapy with tumor-directed T cells is an attractive therapeutic option but has never been evaluated in sarcoma. PATIENTS AND METHODS: We conducted a phase I/II clinical study in which patients with recurrent/refractory human epidermal growth factor receptor 2 (HER2) -positive sarcoma received escalating doses (1 × 10(4)/m(2) to 1 × 10(8)/m(2)) of T cells expressing an HER2-specific chimeric antigen receptor with a CD28...
May 20, 2015: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Jiali Sun, Leslie E Huye, Natalia Lapteva, Maksim Mamonkin, Manasa Hiregange, Brandon Ballard, Olga Dakhova, Darshana Raghavan, April G Durett, Serena K Perna, Bilal Omer, Lisa A Rollins, Ann M Leen, Juan F Vera, Gianpietro Dotti, Adrian P Gee, Malcolm K Brenner, Douglas G Myers, Cliona M Rooney
BACKGROUND: Virus-specific T-cells (VSTs) proliferate exponentially after adoptive transfer into hematopoietic stem cell transplant (HSCT) recipients, eliminate virus infections, then persist and provide long-term protection from viral disease. If VSTs behaved similarly when modified with tumor-specific chimeric antigen receptors (CARs), they should have potent anti-tumor activity. This theory was evaluated by Cruz et al. in a previous clinical trial with CD19.CAR-modified VSTs, but there was little apparent expansion of these cells in patients...
2015: Journal for Immunotherapy of Cancer
Sunandan Saha, Lauren E Woodard, Elizabeth M Charron, Richard C Welch, Cliona M Rooney, Matthew H Wilson
Non-viral transposons have been used successfully for genetic modification of clinically relevant cells including embryonic stem, induced pluripotent stem, hematopoietic stem and primary human T cell types. However, there has been limited evaluation of undesired genomic effects when using transposons for human genome modification. The prevalence of piggyBac(PB)-like terminal repeat (TR) elements in the human genome raises concerns. We evaluated if there were undesired genomic effects of the PB transposon system to modify human cells...
February 18, 2015: Nucleic Acids Research
Julia A Sung, Sharon Lam, Carolina Garrido, Nancie Archin, Cliona M Rooney, Catherine M Bollard, David M Margolis
Enhanced human immunodeficiency virus (HIV)-specific immunity may be required for HIV eradication. Administration of autologous, ex vivo expanded, virus-specific, cytotoxic T-lymphocytes derived from HIV-infected patients on suppressive antiretroviral therapy (HXTCs) are a powerful tool for proof-of-concept studies. Broadly specific, polyclonal HXTCs resulting from ex vivo expansion demonstrated improved control of autologous reservoir virus compared to bulk CD8(+) T cells in viral inhibition assays. Furthermore, patient-derived HXTCs were able to clear latently infected autologous resting CD4(+) T cells following exposure to the latency-reversing agent, vorinostat...
July 15, 2015: Journal of Infectious Diseases
Timothy P Cripe, Minhtran C Ngo, James I Geller, Chrystal U Louis, Mark A Currier, John M Racadio, Alexander J Towbin, Cliona M Rooney, Adina Pelusio, Anne Moon, Tae-Ho Hwang, James M Burke, John C Bell, David H Kirn, Caroline J Breitbach
Pexa-Vec (pexastimogene devacirepvec, JX-594) is an oncolytic and immunotherapeutic vaccinia virus designed to destroy cancer cells through viral lysis and induction of granulocyte-macrophage colony-stimulating factor (GM-CSF)-driven tumor-specific immunity. Pexa-Vec has undergone phase 1 and 2 testing alone and in combination with other therapies in adult patients, via both intratumoral and intravenous administration routes. We sought to determine the safety of intratumoral administration in pediatric patients...
March 2015: Molecular Therapy: the Journal of the American Society of Gene Therapy
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
Sharon Lam, Julia Sung, Conrad Cruz, Paul Castillo-Caro, Minhtran Ngo, Carolina Garrido, Joann Kuruc, Nancie Archin, Cliona Rooney, David Margolis, Catherine Bollard
Antiretroviral therapy (ART) is unable to eradicate human immunodeficiency virus type 1 (HIV-1) infection. Therefore, there is an urgent need to develop novel therapies for this disease to augment anti-HIV immunity. T cell therapy is appealing in this regard as T cells have the ability to proliferate, migrate, and their antigen specificity reduces the possibility of off-target effects. However, past human studies in HIV-1 infection that administered T cells with limited specificity failed to provide ART-independent, long-term viral control...
February 2015: Molecular Therapy: the Journal of the American Society of Gene Therapy
Robert W Lindblad, Laarni Ibenana, John E Wagner, David H McKenna, Derek J Hei, Peiman Hematti, Larry A Couture, Leslie E Silberstein, Myriam Armant, Cliona M Rooney, Adrian P Gee, Lisbeth A Welniak, Traci Heath Mondoro, Deborah A Wood, David Styers
No abstract text is available yet for this article.
March 2015: Transfusion
Jan J Melenhorst, Paul Castillo, Patrick J Hanley, Michael D Keller, Robert A Krance, Judith Margolin, Ann M Leen, Helen E Heslop, A John Barrett, Cliona M Rooney, Catherine M Bollard
A 12-year-old boy with refractory acute lymphoblastic leukemia received a haploidentical transplant from his mother. As prophylaxis for Epstein-Barr virus (EBV), cytomegalovirus (CMV) and adenovirus, he received ex vivo expanded virus-specific donor T cells 3.5 months after transplant. Four weeks later leukemic blasts bearing the E2A deletion, identified by fluorescent in situ hybridization (FISH), appeared transiently in the blood followed by a FISH-negative hematological remission, which was sustained until a testicular relapse 3...
January 2015: Molecular Therapy: the Journal of the American Society of Gene Therapy
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