Read by QxMD icon Read

Chimeric Antigene Receptor

Sinem Civriz Bozdağ, Meltem Kurt Yüksel, Taner Demirer
Stem cells can be either totipotent, pluripotent, multipotent or unipotent. Totipotent cells have the capability to produce all cell types of the developing organism, including both embryonic and extraembryonic tissues. The Hematopoietic Stem Cells (HSC) are the first defined adult stem cells (ASC) that give rise to all blood cells and immune system. Use of HSCs for treatment of hematologic malignancies, which is also called bone marrow (BM) transplantation or peripheral blood stem cells (PBSC) transplantation is the pioneer of cellular therapy and translational research...
March 20, 2018: Advances in Experimental Medicine and Biology
Nan Chen, Xiaoyu Li, Navin K Chintala, Zachary E Tano, Prasad S Adusumilli
Uniform and strong expression of CD19, a cell surface antigen, on cells of B-cell lineage is unique to hematologic malignancies. Tumor-associated antigen (TAA) targets in solid tumors exhibit heterogeneity with regards to intensity and distribution, posing a challenge for chimeric antigen receptor (CAR) T-cell therapy. Novel CAR designs, such as dual TAA-targeted CARs, tandem CARs, and switchable CARs, in conjunction with inhibitory CARs, are being investigated as means to overcome antigen heterogeneity. In addition to heterogeneity in cancer-cell antigen expression, the key determinants for antitumor responses are CAR expression levels and affinity in T cells...
March 16, 2018: Current Opinion in Immunology
Zhongzhen Yi, Brooke L Prinzing, Felicia Cao, Stephen Gottschalk, Giedre Krenciute
Glioblastoma is the most aggressive primary brain tumor in humans and is virtually incurable with conventional therapies. Chimeric antigen receptor (CAR) T cell therapy targeting the glioblastoma antigen EphA2 is an attractive approach to improve outcomes because EphA2 is expressed highly in glioblastoma but only at low levels in normal brain tissue. Building upon our previous findings in this area, we generated and evaluated a panel of EphA2-specific CARs. We demonstrate here that T cells expressing CD28...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
Michael C Milone, Vijay G Bhoj
Adoptive cellular therapy using T cells with tumor specificity derived from either natural T cell receptors (TCRs) or an artificial chimeric antigen receptor (CAR) has reached late phase clinical testing, with two CAR T cell therapies achieving regulatory approval within the United States in 2017. The effective use of these therapies depends upon an understanding of their pharmacology, which is quite divergent from traditional small molecule or biologic drugs. We review the different types of T cell therapy under clinical development, the factors affecting cellular kinetics following infusion, and the relationship between these cellular kinetics and anti-cancer activity...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
F Yang, J Zhang, H Y Qiu, Q Wu, D Q Kong, J J Han, J Q Qi, Y Han, D P Wu
No abstract text is available yet for this article.
January 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Mark Owyong, Gizem Efe, Michael Owyong, Aamna J Abbasi, Vaishnavi Sitarama, Vicki Plaks
There is a growing list of cancer immunotherapeutics approved for use in a population with an increasing number of aged individuals. Cancer immunotherapy (CIT) mediates tumor destruction by activating anti-tumor immune responses that have been silenced through the oncogenic process. However, in an aging individual, immune deregulation is positively correlated with age. In this context, it is vital to examine the age-related changes in the tumor microenvironment (TME) and specifically, those directly affecting critical players to ensure CIT efficacy...
2018: Frontiers in Cell and Developmental Biology
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
Amanda Przespolewski, Andras Szeles, Eunice S Wang
Evasion of the host immune system is a key mechanism to promote malignant progression. Therapeutically targeting immune pathways has radically changed the treatment paradigm for solid and lymphoid tumors but has yet to be approved for myeloid malignancies. Here, we summarize the most recent advances in immunotherapy for acute myeloid leukemia. Topics reviewed here include adoptive cellular approaches (chimeric antigen receptor-T cells, natural killer and other immune cells), checkpoint inhibitors (anti-PD-1/PD-L1, anti-CTLA-4 and TIM-3) and vaccines (WT-1, HLA-A2 and hTERT)...
March 15, 2018: Future Oncology
Nia Emami-Shahri, Julie Foster, Roxana Kashani, Patrycja Gazinska, Celia Cook, Jane Sosabowski, John Maher, Sophie Papa
The unprecedented efficacy of chimeric antigen receptor (CAR) T-cell immunotherapy of CD19+ B-cell malignancy has established a new therapeutic pillar of hematology-oncology. Nonetheless, formidable challenges remain for the attainment of comparable success in patients with solid tumors. To accelerate progress and rapidly characterize emerging toxicities, systems that permit the repeated and non-invasive assessment of CAR T-cell bio-distribution would be invaluable. An ideal solution would entail the use of a non-immunogenic reporter that mediates specific uptake of an inexpensive, non-toxic and clinically established imaging tracer by CAR T cells...
March 14, 2018: Nature Communications
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
Francesco Ceppi, Julie Rivers, Colleen Annesley, Navin Pinto, Julie R Park, Catherine Lindgren, Stephanie Mgebroff, Naomi Linn, Meghan Delaney, Rebecca A Gardner
BACKGROUND: The first step in the production of chimeric antigen receptor T cells is the collection of autologous T cells using apheresis technology. The procedure is technically challenging, because patients often have low leukocyte counts and are heavily pretreated with multiple lines of chemotherapy, marrow transplantation, and/or radiotherapy. Here, we report our experience of collecting T lymphocytes for chimeric antigen receptor T-cell manufacturing in pediatric and young adult patients with leukemia, non-Hodgkin lymphoma, or neuroblastoma...
March 13, 2018: Transfusion
Mei Zhang, Julian A Kim, Alex Yee-Chen Huang
Immunotherapy is revolutionizing cancer treatment. Recent clinical success with immune checkpoint inhibitors, chimeric antigen receptor T-cell therapy, and adoptive immune cellular therapies has generated excitement and new hopes for patients and investigators. However, clinically efficacious responses to cancer immunotherapy occur only in a minority of patients. One reason is the tumor microenvironment (TME), which potently inhibits the generation and delivery of optimal antitumor immune responses. As our understanding of TME continues to grow, strategies are being developed to change the TME toward one that augments the emergence of strong antitumor immunity...
2018: Frontiers in Immunology
Roland B Walter
There is long-standing interest in drugs targeting the myeloid differentiation antigen CD33 in acute myeloid leukemia (AML). Positive results from randomized trials with the antibody-drug conjugate (ADC) gemtuzumab ozogamicin (GO) validate this approach. Partly stimulated by the success of GO, several CD33-targeted therapeutics are currently in early phase testing. Areas covered: CD33-targeted therapeutics in clinical development include Fc-engineered unconjugated antibodies (BI 836858 [mAb 33.1]), ADCs (SGN-CD33A [vadastuximab talirine], IMGN779), radioimmunoconjugates (225 Ac-lintuzumab), bi- and trispecific antibodies (AMG 330, AMG 673, AMV564, 161533 TriKE fusion protein), and chimeric antigen receptor (CAR)-modified immune effector cells...
March 15, 2018: Expert Opinion on Investigational Drugs
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
Anjie Zhen, Christopher W Peterson, Mayra A Carrillo, Sowmya Somashekar Reddy, Cindy S Youn, Brianna B Lam, Nelson Y Chang, Heather A Martin, Jonathan W Rick, Jennifer Kim, Nick C Neel, Valerie K Rezek, Masakazu Kamata, Irvin S Y Chen, Jerome A Zack, Hans-Peter Kiem, Scott G Kitchen
[This corrects the article DOI: 10.1371/journal.ppat.1006753.].
March 2018: PLoS Pathogens
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
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
Kenar D Jhaveri, Mitchell H Rosner
No abstract text is available yet for this article.
March 9, 2018: Clinical Journal of the American Society of Nephrology: CJASN
Kendra C Foley, Michael I Nishimura, Tamson V Moore
Immunotherapy is a promising method of treatment for a number of cancers. Many of the curative results have been seen specifically in advanced-stage melanoma. Despite this, single-agent therapies are only successful in a small percentage of patients, and relapse is very common. As chemotherapy is becoming a thing of the past for treatment of melanoma, the combination of cellular therapies with immunotherapies appears to be on the rise in in-vivo models and in clinical trials. These forms of therapies include tumor-infiltrating lymphocytes, T-cell receptor, or chimeric antigen receptor-modified T cells, cytokines [interleukin (IL-2), IL-15, IL-12, granulocyte-macrophage colony stimulating factor, tumor necrosis factor-α, interferon-α, interferon-γ], antibodies (αPD-1, αPD-L1, αTIM-3, αOX40, αCTLA-4, αLAG-3), dendritic cell-based vaccines, and chemokines (CXCR2)...
March 8, 2018: Melanoma Research
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"