Read by QxMD icon Read

CAR therapy

Hamid Reza Mirzaei, Hossein Pourghadamyari, Majid Rahmati, Abbas Mohammadi, Javid Sadri Nahand, Abbas Rezaei, Hamed Mirzaei, Jamshid Hadjati
Recently clinical trials utilizing genetically engineered T cells expressing a chimeric antigen receptor (CAR) that is half monoclonal antibody and half T-cell receptor have demonstrated remarkable response in patients with advanced cancers like relapsed or refractory acute lymphoblastic leukemia (ALL) and lymphoma. Moreover, emerging chimeric genome editing tools such as zinc-finger nucleases (ZNFs), transcription activator-like effector nucleases (TALENs) and clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas composed of sequence-specific DNA binding module(s) linked to a non-specific DNA cleavage domain have made possible to dramatically expand the ability to manipulate cells aim to treat and/or study a wide range of diseases including cancer...
March 12, 2018: Cancer Letters
Li-Na Zhang, Yongping Song, Delong Liu
The prognosis of adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) remains dismal even at this day and age. With salvage chemotherapy, only 29% (range 18 to 44%) of the patients with R/R ALL can be induced into complete remission (CR), with a median overall survival (OS) of 4 months (range 2-6 months). Blinatumomab and inotuzumab ozogamycin (IO) are immunotherapeutic agents that increased CR to 80% and extended survival to 7.7 months in this high-risk population of patients. In the last few years, chimeric antigen receptor (CAR)--engineered T cells have led to major progress in cancer immunotherapy...
March 15, 2018: Journal of Hematology & Oncology
Pawel Posadzki, Josip Car
Clinical Question: Are light therapies effective and safe for treating acne? Bottom Line: The evidence for all light therapies remains weak and inconclusive. Red-light methyl aminolevulinate-photodynamic therapy (MAL-PDT) was the only treatment associated with a small though clinically insignificant reduction in the number of inflamed lesions and in global improvement as assessed by an investigator in moderate to severe acne. Red-light MAL-PDT was not associated with higher rates of severe adverse effects than placebo or no treatment...
March 14, 2018: JAMA Dermatology
Lisa M Ebert, Wenbo Yu, Tessa Gargett, Michael P Brown
Chimeric antigen receptor (CAR)-T cell therapy has been clinically validated as a curative treatment for the difficult to treat malignancies of relapsed/refractory B-cell acute lymphoblastic leukaemia and lymphoma. Here, the CAR-T cells are re-directed towards a single antigen, CD19, which is recognised as a virtually ideal CAR target antigen because it has strong, uniform expression on cancer cells, and is otherwise expressed only on healthy B cells, which are 'dispensable'. Notwithstanding the clinical success of CD19-CAR-T cell therapy, its single specificity has driven therapeutic resistance in 30% or more of cases with CD19-negative leukaemic relapses...
March 14, 2018: Biochemical Society Transactions
(no author information available yet)
CAR T cells directed against CSPG4 limit the growth of brain tumors in cultured neurospheres and glioma xenograft mouse models, with no signs of immune escape owing to loss of antigen expression.
March 14, 2018: Cancer Discovery
Valerio De Stefano, Alessandra Carobbio, Vincenzo Di Lazzaro, Paola Guglielmelli, Alessandra Iurlo, Maria Chiara Finazzi, Elisa Rumi, Francisco Cervantes, Elena Maria Elli, Maria Luigia Randi, Martin Griesshammer, Francesca Palandri, Massimiliano Bonifacio, Juan-Carlos Hernandez-Boluda, Rossella Cacciola, Palova Miroslava, Giuseppe Carli, Eloise Beggiato, Martin H Ellis, Caterina Musolino, Gianluca Gaidano, Davide Rapezzi, Alessia Tieghi, Francesca Lunghi, Giuseppe Gaetano Loscocco, Daniele Cattaneo, Agostino Cortelezzi, Silvia Betti, Elena Rossi, Guido Finazzi, Bruno Censori, Mario Cazzola, Marta Bellini, Eduardo Arellano-Rodrigo, Irene Bertozzi, Parvis Sadjadian, Nicola Vianelli, Luigi Scaffidi, Montse Gomez, Emma Cacciola, Alessandro M Vannucchi, Tiziano Barbui
We analyzed 597 patients with myeloproliferative neoplasms (MPN) who presented transient ischemic attacks (TIA, n = 270) or ischemic stroke (IS, n = 327). Treatment included aspirin, oral anticoagulants, and cytoreductive drugs. The composite incidence of recurrent TIA and IS, acute myocardial infarction (AMI), and cardiovascular (CV) death was 4.21 and 19.2%, respectively at one and five years after the index event, an estimate unexpectedly lower than reported in the general population. Patients tended to replicate the first clinical manifestation (hazard ratio, HR: 2...
February 28, 2018: Blood Cancer Journal
Carly R Pacanowski, Tyler B Mason, Ross D Crosby, James E Mitchell, Scott J Crow, Stephen A Wonderlich, Carol B Peterson
OBJECTIVE: Treatment for binge eating disorder (BED), a condition associated with both excess adiposity and psychological distress, has not typically produced significant weight loss despite reducing binge eating. Characterizing factors that promote or inhibit weight loss in individuals with co-occurring BED and obesity may help explain overall nonsignificant weight changes during treatment. METHODS: In this study, 189 adults with BED participated in a randomized clinical trial evaluating the efficacy of 5 months of cognitive behavioral therapy...
March 13, 2018: Obesity
Brooke L Prinzing, Stephen M Gottschalk, Giedre Krenciute
The outcome for patients with glioblastoma (GBM) remains poor, and there is an urgent need to develop novel therapeutic approaches. T cells genetically modified with chimeric antigen receptor (CARs) hold the promise to improve outcomes since they recognize and kill cells through different mechanisms than conventional therapeutics. Areas covered: This article reviews CAR design, tumor associated antigens expressed by GBMs that can be targeted with CAR T cells, preclinical and clinical studies conducted with CAR T cells, and genetic approaches to enhance their effector function...
March 13, 2018: Expert Review of Anticancer Therapy
Jahidur Rashid, Kamrun Nahar, Snehal Raut, Ali Keshavarz, Fakhrul Ahsan
We investigated the feasibility of a combination therapy comprising fasudil, a Rho-kinase inhibitor, and DETA NONOate (diethylenetriamine NONOate, DN), a long acting nitric oxide donorboth loaded in liposomes modified with a homing peptide, CAR (CARSKNKDC)in the treatment of pulmonary arterial hypertension (PAH). We first prepared and characterized unmodified- and CAR-modified-liposomes of fasudil and DN. Using individual drugs alone or a mixture of fasudil and DN as controls, we studied the efficacy of the two liposomal preparations in reducing mean pulmonary arterial pressure (mPAP) in monocrotaline (MCT) and SUGEN-hypoxia induced PAH rats...
March 12, 2018: Molecular Pharmaceutics
Jeannine S McCune
Immunotherapy is now the fourth pillar of cancer therapy, with surgery, radiation, and traditional chemotherapy being the remaining pillars. Over the past decade, enthusiasm for immunotherapy has increased because of, in part, data showing that it consistently improves overall survival in select patients with historically refractory cancers. This issue covers various aspects of immunotherapy ranging from use of 1) chimeric antigen receptor (CAR) T cells to treat patients with B-cell acute lymphoblastic leukemia; 2) population pharmacokinetic/dynamic modeling to develop new immune checkpoint inhibitors; and 3) simulations of existing population pharmacokinetic models of immunotherapy to minimize waste without compromising exposure and efficacy...
April 2018: Clinical Pharmacology and Therapeutics
Moomal Tasneem, Carly Mannix, Annette Wong, Jennifer Zhang, Gopala Rangan
The availability of disease-modifying drugs for the management of autosomal dominant polycystic kidney disease (ADPKD) has accelerated the need to accurately predict renal prognosis and/or treatment response in this condition. Arginine vasopressin (AVP) is a critical determinant of postnatal kidney cyst growth in ADPKD. Copeptin (the C-terminal glycoprotein of the precursor AVP peptide) is an accurate surrogate marker of AVP release that is stable and easily measured by immunoassay. Cohort studies show that serum copeptin is correlated with disease severity in ADPKD, and predicts future renal events [decline in renal function and increase in total kidney volume (TKV)]...
March 6, 2018: World Journal of Nephrology
Vishal Jindal
Glioblastoma multiforme (GBM) is the most common primary malignant cancer of brain, which is extremely aggressive and carries a dreadful prognosis. Current treatment protocol runs around radiotherapy, surgical resection, and temozolomide with median overall survival of around 12-15 months. Due to its heterogeneity and mutational load, immunotherapy with chimeric antigen receptor (CAR) T cell therapy can be a promising treatment option for recurrent glioblastoma. Initial phase 1 studies have shown that this therapy is safe without dose-limiting side effects and it also has a better clinical outcome...
March 9, 2018: Molecular Neurobiology
Ciprian Tomuleasa, Shigeo Fuji, Cristian Berce, Anca Onaciu, Sergiu Chira, Bobe Petrushev, Wilhelm-Thomas Micu, Vlad Moisoiu, Ciprian Osan, Catalin Constantinescu, Sergiu Pasca, Ancuta Jurj, Laura Pop, Ioana Berindan-Neagoe, Delia Dima, Shigehisa Kitano
Chimeric antigen receptor (CAR) T-cell technology has seen a rapid development over the last decade mostly due to the potential that these cells may have in treating malignant diseases. It is a generally accepted principle that very few therapeutic compounds deliver a clinical response without treatment-related toxicity, and studies have shown that CAR T-cells are not an exception to this rule. While large multinational drug companies are currently investigating the potential role of CAR T-cells in hematological oncology, the potential of such cellular therapies are being recognized worldwide as they are expected to expand in the patient to support the establishment of the immune memory, provide a continuous surveillance to prevent and/or treat a relapse, and keep the targeted malignant cell subpopulation in check...
2018: Frontiers in Immunology
Albert T Gacerez, Charles L Sentman
Chimeric antigen receptor (CAR) therapy has shown promise against B cell malignancies in the clinic. However, limited success in patients with solid tumors has prompted the development of new CAR strategies. In this study, a B7H6-specific CAR was combined with different variants of T-bet, a transcription factor that acts as the master regulator to induce a Th1 phenotype in CD4+ T cells, to create more effective CAR T cells. Skewing CD4+ CAR T cells into a Th1 improved CAR T cell functional activity while promoting a robust proinflammatory response against B7H6-expressing tumors...
March 7, 2018: Cancer Gene Therapy
Jessica C Petrov, Masayuki Wada, Kevin G Pinz, Lulu E Yan, Kevin H Chen, Xiao Shuai, Hua Liu, Xi Chen, Lai-Han Leung, Huda Salman, Nabil Hagag, Fang Liu, Xun Jiang, Yupo Ma
Acute myeloid leukemia (AML) bears heterogeneous cells that can consequently offset killing by single-CAR-based therapy, which results in disease relapse. Leukemic stem cells (LSCs) associated with CD123 expression comprise a rare population that also plays an important role in disease progression and relapse. Here, we report on the robust anti-tumor activity of a compound CAR (cCAR) T-cell possessing discrete scFv domains targeting two different AML antigens, CD123, and CD33, simultaneously. We determined that the resulting cCAR T-cells possessed consistent, potent, and directed cytotoxicity against each target antigen population...
February 25, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Hisashi Yano, Shin Kaneko
Adoptive cell therapy using tumor-infiltrating T cells has shown durable responses in patients with melanoma, and immunotherapy using genetically engineered T cells (TCR-T or CAR-T) is rapidly emerging as a promising treatment, especially for hematological malignancies. However, the progress is limited because of the lack of readily available good-quality human T cells. Although the efficacy of adoptive cell therapy correlates with the quality of infusing T cells, most antigen-specific T cells in patients with cancer have been exhausted...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Shinichi Kageyama
Cancer immunotherapies using gene-engineered T cells comprise adoptive transfer of T-cell receptor (TCR) and chimeric antigen receptor (CAR) gene-transduced T cells. Although CD19-targeting CAR-T cell therapy is the most progressed, wherein B-cell malignancy is treated efficiently, it also induces cytokine release syndrome and neurotoxicity, which frequently leads to serious adverse events. Of note, TCR-T cell therapy has been primarily used to target melanoma, resulting in 30%-50% of tumor responses. In clinical trials that target NY-ESO-1-expressing synovial sarcoma, a high efficacy of 50%-60% has been obtained...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Stephen J Bagley, Arati S Desai, Gerald P Linette, Carl H June, Donald M O'Rourke
In patients with certain hematologic malignancies, the use of autologous T cells genetically modified to express chimeric antigen receptors (CARs) has led to unprecedented clinical responses. Although progress in solid tumors has been elusive, recent clinical studies have demonstrated the feasibility and safety of CAR T cell therapy for glioblastoma. In addition, despite formidable barriers to T cell localization and effector function in glioblastoma, signs of efficacy have been observed in select patients...
March 2, 2018: Neuro-oncology
Takahiro Kamiya, Desmond Wong, Yi Tian Png, Dario Campana
Practical methods are needed to increase the applicability and efficacy of chimeric antigen receptor (CAR) T-cell therapies. Using donor-derived CAR-T cells is attractive, but expression of endogenous T-cell receptors (TCRs) carries the risk for graft-versus-host-disease (GVHD). To remove surface TCRαβ, we combined an antibody-derived single-chain variable fragment specific for CD3ε with 21 different amino acid sequences predicted to retain it intracellularly. After transduction in T cells, several of these protein expression blockers (PEBLs) colocalized intracellularly with CD3ε, blocking surface CD3 and TCRαβ expression...
March 13, 2018: Blood Advances
Keishi Adachi, Yosuke Kano, Tomohiko Nagai, Namiko Okuyama, Yukimi Sakoda, Koji Tamada
Infiltration, accumulation, and survival of chimeric antigen receptor T (CAR-T) cells in solid tumors is crucial for tumor clearance. We engineered CAR-T cells to express interleukin (IL)-7 and CCL19 (7 × 19 CAR-T cells), as these factors are essential for the maintenance of T-cell zones in lymphoid organs. In mice, 7 × 19 CAR-T cells achieved complete regression of pre-established solid tumors and prolonged mouse survival, with superior anti-tumor activity compared to conventional CAR-T cells. Histopathological analyses showed increased infiltration of dendritic cells (DC) and T cells into tumor tissues following 7 × 19 CAR-T cell therapy...
March 5, 2018: Nature Biotechnology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"