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https://www.readbyqxmd.com/read/28550199/comprehensive-approach-for-identifying-the-t-cell-subset-origin-of-cd3-and-cd28-antibody-activated-chimeric-antigen-receptor-modified-t-cells
#1
Michael Schmueck-Henneresse, Bilal Omer, Thomas Shum, Haruko Tashiro, Maksim Mamonkin, Natalia Lapteva, Sandhya Sharma, Lisa Rollins, Gianpietro Dotti, Petra Reinke, Hans-Dieter Volk, Cliona M Rooney
The outcome of therapy with chimeric Ag receptor (CAR)-modified T cells is strongly influenced by the subset origin of the infused T cells. However, because polyclonally activated T cells acquire a largely CD45RO(+)CCR7(-) effector memory phenotype after expansion, regardless of subset origin, it is impossible to know which subsets contribute to the final T cell product. To determine the contribution of naive T cell, memory stem T cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cell populations to the CD3 and CD28-activated CAR-modified T cells that we use for therapy, we followed the fate and function of individually sorted CAR-modified T cell subsets after activation with CD3 and CD28 Abs (CD3/28), transduction and culture alone, or after reconstitution into the relevant subset-depleted population...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550091/transgenic-expression-of-il15-improves-antiglioma-activity-of-il13ralpha2-car-t-cells-but-results-in-antigen-loss-variants
#2
Giedre Krenciute, Brooke L Prinzing, Zhongzhen Yi, Meng-Fen Wu, Hao Liu, Gianpietro Dotti, Irina V Balyasnikova, Stephen Gottschalk
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and is virtually incurable with conventional therapies. Immunotherapy with T cells expressing GBM-specific chimeric antigen receptors (CARs) is an attractive approach to improve outcomes. Although CAR T cells targeting GBM antigens such as IL13Ralpha2 (interleukin 13 Receptor Subunit Alpha 2), HER2 (human epidermal growth factor receptor 2), and EGFRvIII (epidermal growth factor receptor variant III) have had antitumor activity in preclinical models, early phase clinical testing has demonstrated limited antiglioma activity...
May 26, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28541315/therapeutic-t-cell-engineering
#3
Michel Sadelain, Isabelle Rivière, Stanley Riddell
Genetically engineered T cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimaeric antigen receptors (CARs) are a class of synthetic receptors that reprogram lymphocyte specificity and function. CARs targeting CD19 have demonstrated remarkable potency in B cell malignancies. Engineered T cells are applicable in principle to many cancers, pending further progress to identify suitable target antigens, overcome immunosuppressive tumour microenvironments, reduce toxicities, and prevent antigen escape...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28539557/prospects-for-personalized-combination-immunotherapy-for-solid-tumors-based-on-adoptive-cell-therapies-and-immune-checkpoint-blockade-therapies
#4
Daiki Kato, Tomonori Yaguchi, Takashi Iwata, Kenji Morii, Takayuki Nakagawa, Ryohei Nishimura, Yutaka Kawakami
  Immune checkpoint blockade (ICB) and adoptive cell therapies (ACT) with antigen-receptor gene-engineered T cells have been shown to be successful for a limited number of patients with solid tumors. Responders to ICB therapy typically have T cell-inflamed tumors. Thus, it is important to develop strategies that convert non-T cell-inflamed tumors to T cell-inflamed tumors. Although chimeric antigen receptor transduced T (CAR-T) cell therapy targeting hematological malignancies demonstrated durable clinical responses, the success of gene-engineered T cell therapies in solid tumors is hampered by a lack of unique antigens, antigen loss in cancer cells, and the immune-suppressive tumor microenvironment (TME) of solid tumors...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28539325/cd7-edited-t-cells-expressing-a-cd7-specific-car-for-the-therapy-of-t-cell-malignancies
#5
Diogo Gomes-Silva, Madhuwanti Srinivasan, Sandhya Sharma, Ciaran M Lee, Timothy H Davis, Rayne H Rouce, Gang Bao, Malcolm K Brenner, Maksim Mamonkin
Extending the success of CAR T cells to T-cell malignancies is problematic since most target antigens are shared between normal and malignant cells, leading to CAR T cell fratricide. CD7 is a transmembrane protein highly expressed in acute T cell leukemia (T-ALL) and in a subset of peripheral T-cell lymphomas. Normal expression of CD7 is largely confined to T- and NK cells reducing the risk of off-target-organ toxicity. Here, we show that the expression of a CD7-specific CAR impaired expansion of transduced T cells due to residual CD7 expression and the ensuing fratricide...
May 24, 2017: Blood
https://www.readbyqxmd.com/read/28537234/-car-t-cell-therapy-balance-of-efficacy-and-safety
#6
S V Kulemzin, V V Kuznetsova, M Mamonkin, A V Taranin, A A Gorchakov
Early results from clinical trials of autologous chimeric antigen receptor (CAR)-expressing T cells for the therapy of B-cell malignancies have encouraged extending the potency of this therapy to other cancers. However, the success of using CAR T-cells to treat patients with solid tumors has been limited. In this review, we summarize current knowledge on the design and applications of CARs for the targeted therapy of cancer. We describe existing issues that limit the widespread application of CAR T cells and discuss the optimization steps needed to further improve safety and efficacy of this therapeutic platform...
March 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28536655/supporting-looked-after-children-and-care-leavers-in-decreasing-drugs-and-alcohol-solid-protocol-for-a-pilot-feasibility-randomised-controlled-trial-of-interventions-to-decrease-risky-substance-use-drugs-and-alcohol-and-improve-mental-health-of-looked-after
#7
Hayley Alderson, Ruth McGovern, Rebecca Brown, Denise Howel, Frauke Becker, Louise Carr, Alex Copello, Tony Fouweather, Eileen Kaner, Paul McArdle, Elaine McColl, Janet Shucksmith, Alison Steele, Luke Vale, Raghu Lingam
BACKGROUND: Looked after children (LAC) and care leavers are young people who have been placed under the legal care of local authorities, in many instances due to a history of abuse and/or neglect. These young people have a significantly increased risk of substance use and mental disorder compared to their peers. The aim of the SOLID study is to assess the feasibility and acceptability of a definitive three-arm multi-centre randomised controlled trial (RCT) that compares the effectiveness of two interventions that aim to reduce risky drug and alcohol use and improve mental health among LAC aged 12 to 20 years with usual care...
2017: Pilot and Feasibility Studies
https://www.readbyqxmd.com/read/28529898/preclinical-rationale-for-combining-radiation-therapy-and-immunotherapy-beyond-checkpoint-inhibitors-i-e-cart
#8
REVIEW
James P Flynn, Mark H O'Hara, Saumil J Gandhi
An increasing appreciation for the role of the immune system in targeting cancer cells over the last decade has led to the development of several immunomodulatory agents aimed at enhancing the systemic antitumor immune response. One such method is the use of T cells that are genetically engineered to express chimeric antigen receptors (CARs). The remarkable success of this approach in advanced hematologic malignancies has garnered much enthusiasm for using this novel tool in treating other cancers. However, multiple challenges have hampered the application of this therapy to a broader set of solid tumors, most notably lung cancer...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28528746/car-t-cell-therapy-effective-in-b-acute-lymphoblastic-leukaemia
#9
Mai Wang
No abstract text is available yet for this article.
May 18, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28514768/driving-better-and-safer-her2-specific-cars-for-cancer-therapy
#10
REVIEW
Xianqiang Liu, Nan Zhang, Huan Shi
Given the clinical efficacy of chimeric antigen receptor (CAR)-based therapy in hematological malignancies, CAR T-cell therapy for a number of solid tumors has been actively investigated. Human epidermal growth factor receptor 2 (HER2) is a well-established therapeutic target in breast, as well as other types of cancer. However, HER2 CAR T cells pose a risk of lethal toxicity including cytokine release syndrome from "on-target, off-tumor" recognition of HER2. In this review, we summarize the development of conventional HER2 CAR technology, the alternative selection of CAR hosts, the novel HER2 CAR designs, clinical studies and toxicity...
April 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512692/virtual-reality-enhanced-extinction-of-phobias-and-post-traumatic-stress
#11
REVIEW
Jessica L Maples-Keller, Carly Yasinski, Nicole Manjin, Barbara Olasov Rothbaum
Virtual reality (VR) refers to an advanced technological communication interface in which the user is actively participating in a computer-generated 3-dimensional virtual world that includes computer sensory input devices used to simulate real-world interactive experiences. VR has been used within psychiatric treatment for anxiety disorders, particularly specific phobias and post-traumatic stress disorder, given several advantages that VR provides for use within treatment for these disorders. Exposure therapy for anxiety disorder is grounded in fear-conditioning models, in which extinction learning involves the process through which conditioned fear responses decrease or are inhibited...
May 16, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28511045/stigma-and-diurnal-cortisol-among-transitioning-transgender-men
#12
L Zachary DuBois, Sally Powers, Bethany G Everett, Robert-Paul Juster
This study assessed diurnal cortisol functioning in relation to stigma-based transition-specific stressors experienced by transgender men during their transition from female to male. Sixty-five healthy transgender men undergoing testosterone therapy participated in in-person interviews through which transition-specific stressors were identified. Interviews were coded according to participant reported (1) Transitioning-identity stress; (2) Coming Out stress; (3) Gender-specific Public Bathroom stress; and (4) levels of general Perceived Stress...
May 8, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28506444/monocyte-lineage-derived-il-6-does-not-affect-chimeric-antigen-receptor-t-cell-function
#13
Nathan Singh, Ted J Hofmann, Zachary Gershenson, Bruce L Levine, Stephan A Grupp, David T Teachey, David M Barrett
BACKGROUND AIMS: Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has demonstrated remarkable success in targeting B-cell malignancies but is often complicated by serious systemic toxicity in the form of cytokine release syndrome (CRS). CRS symptoms are primarily mediated by interleukin 6 (IL-6), and clinical management has focused on inhibition of IL-6 signaling. The cellular source and function of IL-6 in CRS remain unknown. METHODS: Using co-culture assays and data from patients on our clinical CAR T-cell trials, we investigated the cellular source of IL-6, as well as other CRS-associated cytokines, during CAR T-cell activation...
May 11, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28502785/car-t-cell-therapy-for-lung-cancer-and-malignant-pleural-mesothelioma
#14
REVIEW
Masha Zeltsman, Jordan Dozier, Erin McGee, Daniel Ngai, Prasad S Adusumilli
Immunotherapy is a promising field that harnesses the power of the immune system as a therapeutic agent for cancer treatment. Beneficial outcomes shown in patients with non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM) with relatively higher tumor-infiltrating T cells, combined with impressive responses obtained in a cohort of patients with NSCLC following checkpoint blockade therapy, lays a strong foundation to promote effector immune responses in these patients. One such approach being investigated is administration of tumor antigen-targeted T cells with transduction of a chimeric antigen receptor (CAR)...
April 26, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28497159/current-status-of-chimeric-antigen-receptor-engineered-t-cell-based-and-immune-checkpoint-blockade-based-cancer-immunotherapies
#15
REVIEW
Upendra P Hegde, Bijay Mukherji
Adoptive cell therapies with chimeric antigen receptor (CAR) engineered T cells (CAR-T) and immune checkpoint inhibition (ICI)-based cancer immunotherapies have lately shown remarkable success in certain tumor types. CAR-T cell-based therapies targeting CD19 can now induce durable remissions as well as prolong disease-free survival of patients with CD19 positive treatment refractory B cell malignancies and ICI-based therapies with humanized monoclonal antibodies against the T cell inhibitory receptors CTLA-4 and PD-1 as well as against the PD-1 ligand, PD-L1, can now achieve durable remissions as well as prolongation of life of a sizeable fraction of patients with melanoma and Hodgkin's lymphoma and non-small cell cancers...
May 11, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28490811/high-efficacy-and-safety-of-low-dose-cd19-directed-car-t-cell-therapy-in-51-refractory-or-relapsed-b-acute-lymphoblastic-leukemia-patients
#16
J Pan, J Yang, B Deng, X Zhao, X Zhang, Y Lin, Y Wu, Z Deng, Y Zhang, S Liu, T Wu, P Lu, D Lu, A H Chang, C Tong
Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD(+)) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T cell infusion dosages were initially ranged from 0.05 to 14 × 10(5)/kg and were eventually settled at 1 × 10(5)/kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD(+) patients achieved MRD(-)...
May 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28488799/systematic-review-of-exercise-training-in-colorectal-cancer-patients-during-treatment
#17
REVIEW
Stefanus J van Rooijen, Maartje A Engelen, Celena Scheede-Bergdahl, Francesco Carli, Rudi Mh Roumen, Gerrit D Slooter, Goof Schep
INTRODUCTION: Colorectal cancer surgery results in considerable postoperative morbidity, mortality and reduced quality of life. Since many patients will undergo additional (neo)adjuvant therapy, it is imperative that each individual optimize their physical function. To elucidate the potential of exercise in patient optimization, we investigated the evidence for an exercise program before and after surgical treatment in colorectal cancer patients. METHODS: A systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions, the guidelines of the Physical Therapy Journal and the PRISMA guidelines...
May 10, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28484827/-hot-rods-in-the-icu-what-is-the-antibiotic-mileage-of-your-renal-replacement-therapy
#18
REVIEW
J T Kielstein, A K Kruse, N Anderson, H Vaitiekunas, S Scherneck
We would neither be disappointed nor upset if the gas mileage on the sticker of a car didn't match our personal, real-life fuel consumption. Depending on our daily route to work, our style of accelerating and the number of passengers in our carpool, the gas mileage will vary. As soon as the falcon wing door of our car is closed and entrance to the ICU is granted, we tend to forget all of this, even though another hot rod is waiting there for us. Renal replacement therapy is like a car; it fulfills goals, such as the removal of uremic toxins and accumulated fluids, but it also "consumes" (removes) antibiotics...
May 8, 2017: Medizinische Klinik, Intensivmedizin und Notfallmedizin
https://www.readbyqxmd.com/read/28483281/preclinical-data-support-leveraging-cs1-chimeric-antigen-receptor-t-cell-therapy-for-systemic-light-chain-amyloidosis
#19
Michael Rosenzweig, Ryan Urak, Miriam Walter, Laura Lim, James F Sanchez, Amrita Krishnan, Stephen Forman, Xiuli Wang
BACKGROUND AIMS: Light chain amyloidosis (AL) is a protein deposition disorder that is a result of a plasma cell dyscrasia, similar to multiple myeloma (MM). Immunotherapy is an attractive approach because of the low burden of disease, but the optimal target for AL is unclear. CS1 and B-cell maturation antigen (BCMA) are two potential targets because they are expressed on normal plasma cells and MM cells. METHODS: We performed a prospective study evaluating bone marrow specimens of 20 patients with plasma cell diseases, 10 with AL and 10 with MM...
May 5, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28482671/advances-in-evidence-based-cancer-adoptive-cell-therapy
#20
Chunlei Ge, Ruilei Li, Xin Song, Shukui Qin
Adoptive cell therapy (ACT) has been developed in cancer treatment by transferring/infusing immune cells into cancer patients, which are able to recognize, target, and destroy tumor cells. Recently, sipuleucel-T and genetically-modified T cells expressing chimeric antigen receptors (CAR) show a great potential to control metastatic castration-resistant prostate cancer and hematologic malignancies in clinic. This review summarized some of the major evidence-based ACT and the challenges to improve cell quality and reduce the side effects in the field...
April 2017: Chinese Clinical Oncology
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