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https://www.readbyqxmd.com/read/29032736/coccidioidomycosis-immunoglobulin-deficiency-safety-challenges-with-car-t-cells-therapy-for-relapsed-lymphoma
#1
Umar Zahid, Al-Aman Shaukat, Nida Hassan, Faiz Anwer
Treatment of patients with relapsed or refractory lymphoma may require allogenic hematopoietic stem cell transplant (HSCT), but treatment of post-transplant relapse disease remains very challenging. Donor lymphocyte infusion and blinatumomab have been used with limited success for the treatment of relapse. Initial data on donor-derived CAR T cells has shown this modality to be safe and highly effective in various hematological malignancies. We present a case of a patient with highly refractory, transformed follicular lymphoma who failed both autologous and allogenic HSCT...
October 2017: Immunotherapy
https://www.readbyqxmd.com/read/29032733/car-t-cells-and-allogeneic-hematopoietic-stem-cell-transplantation-for-relapsed-refractory-b-cell-acute-lymphoblastic-leukemia
#2
Jun Liu, Xi Zhang, Jiang F Zhong, Cheng Zhang
Relapsed/refractory acute lymphoblastic leukemia (ALL) has a low remission rate after chemotherapy, a high relapse rate and poor long-term survival even when allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed. Chimeric antigen receptors redirected T cells (CAR-T cells) can enhance disease remission with a favorable outcome for relapsed/refractory ALL, though some cases quickly relapsed after CAR-T cell treatment. Thus, treatment with CAR-T cells followed by allo-HSCT may be the best way to treat relapsed/refractory ALL...
October 2017: Immunotherapy
https://www.readbyqxmd.com/read/29032264/building-a-safer-and-faster-car-seatbelts-airbags-and-crispr
#3
REVIEW
Miguel-Angel Perales, Partow Kebriaei, Leslie S Kean, Michel Sadelain
Therapeutic T cell engineering has recently garnered widespread interest owing to the success of CD19 (Chimeric Antigen Receptor) CAR therapy. CARs are synthetic receptors for antigen that redirect the specificity and reprogram the function of the T cells in which they are genetically introduced. CARs targeting CD19, a cell surface molecule found in most leukemias and lymphomas, have yielded high remission rates in patients with chemorefractory, relapsed disease, including acute lymphoblastic leukemia, chronic lymphocytic leukemia and non-Hodgkin lymphoma...
October 12, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29029813/innovative-therapy-monoclonal-antibodies-and-beyond
#4
M Di Nicola, L Apetoh, M Bellone, M P Colombo, G Dotti, S Ferrone, M Muscolini, J Hiscott, A Anichini, S M Pupa, F de Braud, M Del Vecchio
The seventh Edition of "Innovative Therapy, Monoclonal Antibodies and Beyond" Meeting took place in Milan, Italy, on January 27, 2017. The two sessions of the meeting were focused on: 1) Preclinical assays and novel biotargets; and 2) monoclonal antibodies, cell therapies and targeted molecules. Between these two sessions, a lecture entitled "HLA-antigens modulation and response to immune checkpoint inhibitor immunotherapy" was also presented. Despite the impressive successes in cancer immunotherapy in recent years, the response to immune based interventions occurs only in a minority of patients (∼20%)...
October 5, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29029499/generation-and-characterization-of-erbb2-car-engineered-cytokine-induced-killer-cells-for-the-treatment-of-high-risk-soft-tissue-sarcoma-in-children
#5
Michael Merker, Verena Pfirrmann, Sarah Oelsner, Simone Fulda, Thomas Klingebiel, Winfried S Wels, Peter Bader, Eva Rettinger
Pediatric patients with recurrent, refractory or advanced soft tissue sarcoma (STS) who are simultaneously showing signs of cumulative treatment toxicity are in need of novel therapies. In this preclinical analysis, we identified ErbB2 as a targetable antigen on STS cells and used cytokine-induced killer (CIK) cells transduced with the lentiviral 2(nd)-generation chimeric antigen receptor (CAR) vector pS-5.28.z-IEW to target ErbB2-positive tumors. Solely CIK cell subsets with the CD3(+) T cell phenotype showed up to 85% cell surface expression of the respective CAR...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29025771/endothelial-activation-and-blood-brain-barrier-disruption-in-neurotoxicity-after-adoptive-immunotherapy-with-cd19-car-t-cells
#6
Juliane Gust, Kevin A Hay, Laïla-Aïcha Hanafi, Daniel Li, David Myerson, Luis F Gonzalez-Cuyar, Cecilia Yeung, W Conrad Liles, Mark Wurfel, Jose A Lopez, Junmei Chen, Dominic Chung, Susanna Harju-Baker, Tahsin Özpolat, Kathleen R Fink, Stanley R Riddell, David G Maloney, Cameron J Turtle
Lymphodepletion chemotherapy followed by infusion of CD19-targeted chimeric antigen receptor-modified T (CAR-T) cells can be complicated by neurologic adverse events (AE) in patients with refractory B-cell malignancies. In 133 adults treated with CD19 CAR-T cells, we found that acute lymphoblastic leukemia, high CD19(+) cells in bone marrow, high CAR-T cell dose, cytokine release syndrome, and preexisting neurologic comorbidities were associated with increased risk of neurologic AEs. Patients with severe neurotoxicity demonstrated evidence of endothelial activation, including disseminated intravascular coagulation, capillary leak, and increased blood-brain barrier (BBB) permeability...
October 12, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29025766/car-t-therapy-targeting-icam-1-eliminates-advanced-human-thyroid-tumors
#7
Irene M Min, Enda Shevlin, Yogindra Vedvyas, Marjan Zaman, Brian Wyrwas, Theresa Scognamiglio, Maureen D Moore, Weibin Wang, Susan Park, Spencer Park, Suraj Panjwani, Katherine D Gray, Andrew B Tassler, Rasa Zarnegar, Thomas J Fahey, Moonsoo M Jin
PURPOSE: Poorly-differentiated thyroid cancer and anaplastic thyroid cancer (ATC) are rare yet lethal malignancies with limited treatment options. Many malignant tumors including papillary thyroid cancer (PTC) and ATC are associated with increased expression of ICAM-1, providing a rationale for utilizing ICAM-1-targeting agents for the treatment of aggressive cancer. We developed a third-generation CAR targeting ICAM-1 to leverage adoptive T cell therapy as a new treatment modality. EXPERIMENTAL DESIGN: ICAM-1 CAR T cells were applied on multiple malignant and non-malignant target cells to investigate specific target cell death and 'off-tumor' toxicity in vitro...
October 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29025266/the-abcs-of-immunotherapy-for-adult-patients-with-b-cell-acute-lymphoblastic-leukemia
#8
Troy Z Horvat, Amanda N Seddon, Adebayo Ogunniyi, Amber C King, Larry W Buie, Ryan J Daley
OBJECTIVE: To review the pharmacology, efficacy, and safety of Food and Drug Administration approved and promising immunotherapy agents used in the treatment of acute lymphoblastic leukemia (ALL). DATA SOURCES: A literature search was performed of PubMed and MEDLINE databases (1950 to July 2017) and of abstracts from the American Society of Hematology and the American Society of Clinical Oncology. Searches were performed utilizing the following key terms: rituximab, blinatumomab, inotuzumab, ofatumumab, obinutuzumab, Blincyto, Rituxan, Gazyva, Arzerra, CAR T-cell, and chimeric antigen receptor (CAR)...
October 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29024301/emerging-principles-from-the-clinical-application-of-chimeric-antigen-receptor-car-t-cell-therapies-for-b-cell-malignancies
#9
REVIEW
Michael D Jain, Marco L Davila
Gene-engineered T cell therapies are soon to be FDA approved for at least two types of B cell malignancies in pediatric and adult patients, in the form of CD19 targeted chimeric antigen receptor T (CAR T) cell therapy. This represents a triumph of a true bench to bedside clinical translation of a therapy that was conceived of in the early 1990s. Clinical results have demonstrated efficacious responses in patients with the CD19 positive diseases B cell acute lymphoblastic leukemia (B-ALL) and diffuse large B cell lymphoma (DLBCL)...
October 11, 2017: Stem Cells
https://www.readbyqxmd.com/read/29023549/supraphysiologic-control-over-hiv-1-replication-mediated-by-cd8-t-cells-expressing-a-re-engineered-cd4-based-chimeric-antigen-receptor
#10
Rachel S Leibman, Max W Richardson, Christoph T Ellebrecht, Colby R Maldini, Joshua A Glover, Anthony J Secreto, Irina Kulikovskaya, Simon F Lacey, Sarah R Akkina, Yanjie Yi, Farida Shaheen, Jianbin Wang, Keith A Dufendach, Michael C Holmes, Ronald G Collman, Aimee S Payne, James L Riley
HIV is adept at avoiding naturally generated T cell responses; therefore, there is a need to develop HIV-specific T cells with greater potency for use in HIV cure strategies. Starting with a CD4-based chimeric antigen receptor (CAR) that was previously used without toxicity in clinical trials, we optimized the vector backbone, promoter, HIV targeting moiety, and transmembrane and signaling domains to determine which components augmented the ability of T cells to control HIV replication. This re-engineered CAR was at least 50-fold more potent in vitro at controlling HIV replication than the original CD4 CAR, or a TCR-based approach, and substantially better than broadly neutralizing antibody-based CARs...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29017060/integrating-proteomics-and-transcriptomics-for-systematic-combinatorial-chimeric-antigen-receptor-therapy-of-aml
#11
Fabiana Perna, Samuel H Berman, Rajesh K Soni, Jorge Mansilla-Soto, Justin Eyquem, Mohamad Hamieh, Ronald C Hendrickson, Cameron W Brennan, Michel Sadelain
Chimeric antigen receptor (CAR) therapy targeting CD19 has yielded remarkable outcomes in patients with acute lymphoblastic leukemia. To identify potential CAR targets in acute myeloid leukemia (AML), we probed the AML surfaceome for overexpressed molecules with tolerable systemic expression. We integrated large transcriptomics and proteomics datasets from malignant and normal tissues, and developed an algorithm to identify potential targets expressed in leukemia stem cells, but not in normal CD34(+)CD38(-) hematopoietic cells, T cells, or vital tissues...
October 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29016929/trivalent-car-t-cells-overcome-interpatient-antigenic-variability-in-glioblastoma
#12
Kevin Bielamowicz, Kristen Fousek, Tiara T Byrd, Hebatalla Samaha, Malini Mukherjee, Nikita Aware, Meng-Fen Wu, Jordan S Orange, Pavel Sumazin, Tsz-Kwong Man, Sujith K Joseph, Meenakshi Hegde, Nabil Ahmed
Background: Glioblastoma (GBM) is the most common primary malignant brain cancer, and is currently incurable. Chimeric Antigen Receptor (CAR) T-cells have shown promise in GBM treatment. While we have shown that combinatorial targeting of two glioma antigens offsets antigen escape and enhances T-cell effector functions, the inter-patient variability in surface antigen expression between patients hinders the clinical impact of targeting two antigen pairs. This study addresses targeting 3 antigens using a single CAR T-cell product for broader application...
September 16, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28993773/targeting-malignant-brain-tumors-with-antibodies
#13
REVIEW
Rok Razpotnik, Neža Novak, Vladka Čurin Šerbec, Uros Rajcevic
Antibodies have been shown to be a potent therapeutic tool. However, their use for targeting brain diseases, including neurodegenerative diseases and brain cancers, has been limited, particularly because the blood-brain barrier (BBB) makes brain tissue hard to access by conventional antibody-targeting strategies. In this review, we summarize new antibody therapeutic approaches to target brain tumors, especially malignant gliomas, as well as their potential drawbacks. Many different brain delivery platforms for antibodies have been studied such as liposomes, nanoparticle-based systems, cell-penetrating peptides (CPPs), and cell-based approaches...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28988742/chimeric-antigen-receptor-t-cell-therapy-for-hematological-malignancies-and-solid-tumors-clinical-data-to-date-current-limitations-and-perspectives
#14
REVIEW
J Gauthier, I Yakoub-Agha
Progress in our understanding of basic immunology along with the advent of bioengineering technologies have made possible the production of human T-cells expressing Chimeric Antigen Receptors (CAR T-cells). These CAR T-cells are designed to target specific antigens presented by cancer cells. Once CARs are bound to these antigens, CAR T-cells get activated and can initiate potent anti-tumor effects. We will here overview the bioengineering advances which made possible the clinical application of CAR T-cell therapy...
October 5, 2017: Current Research in Translational Medicine
https://www.readbyqxmd.com/read/28983300/human-tregs-made-antigen-specific-by-gene-modification-the-power-to-treat-autoimmunity-and-antidrug-antibodies-with-precision
#15
REVIEW
Patrick R Adair, Yong Chan Kim, Ai-Hong Zhang, Jeongheon Yoon, David W Scott
Human regulatory CD4(+) T cells (Tregs) are potent immunosuppressive lymphocytes responsible for immune tolerance and homeostasis. Since the seminal reports identifying Tregs, vast research has been channeled into understanding their genesis, signature molecular markers, mechanisms of suppression, and role in disease. This research has opened the doors for Tregs as a potential therapeutic for diseases and disorders such as multiple sclerosis, type I diabetes, transplantation, and immune responses to protein therapeutics, like factor VIII...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28978841/treatment-of-relapsed-or-refractory-acute-lymphoblastic-leukemia
#16
Kiyotoshi Imai
Most patients with adult acute lymphoblastic leukemia (ALL) undergo relapse, despite the achievement of complete remission with chemotherapy. Among patients with relapsed or refractory ALL, remission rates are 18-44% with the use of standard salvage chemotherapy, but the duration of remission is short. A major goal in this population is to induce remission with a sufficient duration to prepare for stem cell transplantation. The poor outcomes and lack of durable responses seen with conventional chemotherapy have led to the development of several novel agents, including clofarabine and nelarabine...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28978471/tonic-4-1bb-costimulation-in-chimeric-antigen-receptors-impedes-t-cell-survival-and-is-vector-dependent
#17
Diogo Gomes-Silva, Malini Mukherjee, Madhuwanti Srinivasan, Giedre Krenciute, Olga Dakhova, Yueting Zheng, Joaquim M S Cabral, Cliona M Rooney, Jordan S Orange, Malcolm K Brenner, Maksim Mamonkin
Antigen-independent tonic signaling by chimeric antigen receptors (CARs) can increase differentiation and exhaustion of T cells, limiting their potency. Incorporating 4-1BB costimulation in CARs may enable T cells to resist this functional exhaustion; however, the potential ramifications of tonic 4-1BB signaling in CAR T cells remain unclear. Here, we found that tonic CAR-derived 4-1BB signaling can produce toxicity in T cells via continuous TRAF2-dependent activation of the nuclear factor κB (NF-κB) pathway and augmented FAS-dependent cell death...
October 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28978241/treating-hematological-malignancies-with-cell-therapy-where-are-we-now
#18
Elisa Landoni, Barbara Savoldo
Adoptive cell therapy (ACT) is becoming an increasingly successful and widespread form of treatment for different types of cancer. Compared to chemotherapy or monoclonal antibodies, ACT is an active biological strategy, with infused immune cells featuring dynamic migration, expansion and long-term persistence properties. ACT in hematological malignancies offered the initial proof of principle of the feasibility for this innovative 'live-drug'. Areas covered: In this review, the authors summarize the clinical results achieved with two specific strategies in hematological malignancies: chimeric antigen receptor (CAR) and T cell receptor (transgenic TCR) redirected T cells...
October 5, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28977984/driving-better-and-safer-her2-specific-cars-for-cancer-therapy
#19
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...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975930/immunotherapy-tisagenlecleucel-the-first-approved-car-t-cell-therapy-implications-for-payers-and-policy-makers
#20
Vinay Prasad
No abstract text is available yet for this article.
October 4, 2017: Nature Reviews. Clinical Oncology
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