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Serena Delbue, Manola Comar, Pasquale Ferrante
Natalizumab is a monoclonal antibody directed against the α4 chain of the very late activating antigen 4 and α4β7 integrins, present on the leukocytes surface, used as monotherapy for the treatment of relapsing-remitting multiple sclerosis. It substantially reduces relapse rate and the accumulation of disability, but its use is associated with a very adverse event, that is the development of progressive multifocal leukoencephalopathy, a fatal demyelinating disease of the CNS, due to the lytic replication of the human polyomavirus JC...
December 22, 2016: Immunotherapy
Yiqun Zhou, Xiaolan Li, Yun Liu, Qiquan Sun
Antibody-mediated rejection (AMR) is a pivotal cause of long-term graft failure following renal transplantation. De novo donor-specific antibody reduction is essential to prevent AMR and improve long-term graft survival in renal transplant recipients. Although the number of early AMR episodes can be successfully controlled by attenuating de novo donor-specific antibodies, the long-term outcomes are unsatisfactory. Numerous studies have focused on new strategies to reverse AMR, but the available evidence suggests that maintenance immunosuppressive agents play important roles...
January 2017: Immunotherapy
Adam J Adler, Payal Mittal, Joseph M Ryan, Beiyan Zhou, Jeffrey S Wasser, Anthony T Vella
Recent advances in cancer biology and genetics have fostered precision therapies targeting tumor-specific attributes. Immune-based therapies that elicit cytolytic T cells (CTL) specific for tumor antigens can provide therapeutic benefit to cancer patients, however, cure rates are typically low. This largely results from immunosuppressive mechanisms operating within the tumor microenvironment, many of which inflict metabolic stresses upon CTL. Conversely, immunotherapies can mitigate specific metabolic stressors...
January 2017: Immunotherapy
Sonia Mannan
No abstract text is available yet for this article.
January 2017: Immunotherapy
(no author information available yet)
No abstract text is available yet for this article.
January 2017: Immunotherapy
Giandomenico Roviello, Laura Zanotti, Pierpaolo Correale, Angela Gobbi, Simon Wigfield, Alessandra Guglielmi, Chiara Pacifico, Daniele Generali
AIM: IL-2 is one of the first immunomodulating cytokines to be tested in the treatment of cancer patients. The effects of this agent in the treatment of solid tumors other than renal cancer and melanoma are poorly understood. MATERIALS & METHODS: We have carried out a meta-analysis of randomized studies. We fixed the response rate as the primary outcome. RESULTS: The pooled risk ratio for an objective response with IL-2 plus chemotherapy versus chemotherapy alone was 1...
January 2017: Immunotherapy
Mahmoud A Ali, Marwa Matboli, Marwa Tarek, Maged Reda, Kamal M Kamal, Mahmoud Nouh, Ahmed M Ashry, Ahmed Fath El-Bab, Hend A Mesalam, Ayman El-Sayed Shafei, Omar Abdel-Rahman
Epigenetic changes in oncogenes and tumor-suppressor genes contribute to carcinogenesis. Understanding the epigenetic and genetic components of tumor immune evasion is crucial. Few cancer genetic mutations have been linked to direct correlations with immune evasion. Studies on the epigenetic modulation of the immune checkpoints have revealed a critical interaction between epigenetic and immune modulation. Epigenetic modifiers can activate many silenced genes. Some of them are immune checkpoints regulators that turn on immune responses and others turn them off resulting in immune evasion...
January 2017: Immunotherapy
Ksenia Bezverbnaya, Ashish Mathews, Jesse Sidhu, Christopher W Helsen, Jonathan L Bramson
Immunotherapy with chimeric antigen receptor (CAR) T cells has been advancing steadily in clinical trials. Since the ability of engineered T cells to recognize intended tumor-associated targets is crucial for the therapeutic success, antigen-binding domains play an important role in shaping T-cell responses. Single-chain antibody and T-cell receptor fragments, natural ligands, repeat proteins, combinations of the above and universal tag-specific domains have all been used in the antigen-binding moiety of chimeric receptors...
January 2017: Immunotherapy
Laura C Cappelli, Jarushka Naidoo, Clifton O Bingham, Ami A Shah
No abstract text is available yet for this article.
January 2017: Immunotherapy
Elina Timosenko, Andreas V Hadjinicolaou, Vincenzo Cerundolo
To evade immune destruction, tumors exploit a wide range of immune escape mechanisms, including the induction of an immunosuppressive tumor microenvironment. This is mediated, in part, by amino acid degrading enzymes indoleamine 2,3-dioxygenase, tryptophan 2,3-dioxygenase, arginase 1 and arginase 2, which have emerged as key players in the regulation of tumor-induced immune tolerance. Here we describe how the expression of tryptophan- and arginine-degrading enzymes by tumor and tumor-infiltrating cells can hamper cancer-specific immune responses, and discuss how this knowledge is being exploited to develop new strategies for cancer immunotherapy...
January 2017: Immunotherapy
Jennifer P Morton, Owen J Sansom
No abstract text is available yet for this article.
January 2017: Immunotherapy
Warren Greth, Gabriel J Robbie, Philip Brohawn, Micki Hultquist, Bing Yao
Dysregulation of the type I interferon (IFN) system is associated with various immunologic diseases, such as systemic lupus erythematosus (SLE). Targeting this dysregulation presents an attractive approach for SLE therapy. Sifalimumab, a fully human immunoglobulin G1 κ monoclonal antibody that binds to and neutralizes most IFN-α subtypes, has been recently evaluated in a Phase IIb study in patients with moderate to severe SLE. Insights gained from earlier studies were used to inform design of the Phase IIb study, to provide a more comprehensive evaluation of sifalimumab...
January 2017: Immunotherapy
Uyanga Batbold, Dmytro O Butov, Galyna A Kutsyna, Narantsetseg Damdinpurev, Elena A Grinishina, Otgonbayar Mijiddorj, Mikola E Kovolev, Khaliunaa Baasanjav, Tatyana S Butova, Munkhburam Sandagdorj, Ochirbat Batbold, Ariungerel Tseveendorj, Erkhemtsetseg Chunt, Svetlana I Zaitzeva, Hanna L Stepanenko, Natalia I Makeeva, Igor V Mospan, Volodymyr S Pylypchuk, John L Rowe, Peter Nyasulu, Vichai Jirathitikal, Allen I Bain, Marina G Tarakanovskaya, Aldar S Bourinbaiar
AIM: Safer and shorter antituberculosis treatment (ATT) regimens represent the unmet medical need. PATIENTS & METHODS: The patients were randomly assigned into two arms: the first (n = 137) received once-daily sublingual honey lozenge formulated with botanical immunomodulator Immunoxel and the second (n = 132) received placebo lozenges along with conventional ATT. Immunoxel and placebo arms were demographically similar: 102 versus 106 had drug-susceptible TB; 28 versus 20 multidrug-resistant TB (MDR-TB); 7 versus 7 extensively drug-resistant TB (XDR-TB); and 22 versus 20 TB-HIV...
January 2017: Immunotherapy
John Girdlestone
Mesenchymal stromal cells (MSC) are connective tissue progenitor cells with interesting immunoregulatory properties and are currently being assessed as cellular therapeutics in a variety of clinical applications. While bone marrow has been the traditional source, adipose tissue and umbilical cord are being used increasingly to generate MSC for therapeutic use as an allogeneic, off-the-shelf product. Although the means by which MSC home to sites of inflammation or tissue damage and exert their beneficial effects remain to be fully elucidated, they have recently been shown to adsorb a number of immunosuppressive and anticancer drugs that may further enhance their therapeutic potential...
December 2016: Immunotherapy
Matteo Simonelli, Luca Di Tommaso, Marina Baretti, Armando Santoro
Immune checkpoint inhibitors such as anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies have dramatically changed the paradigm of cancer therapy over the past few years. The use of these agents is associated with a unique pattern of autoimmune-like/inflammatory side effects termed immune-related adverse events (irAEs), that may cause collateral damage to normal tissues. Although severe irAEs remain rare, they can become life-threatening if not anticipated and managed appropriately. Improving our knowledge of the mechanisms underlying the development of these toxicities is crucial to optimize clinical efficacy and safety of these new immunotherapeutics...
December 2016: Immunotherapy
Elie El Rassy, Hampig R Kourie, Jamale Rizkallah, Fadi El Karak, Colette Hanna, Dania N Chelala, Marwan Ghosn
The choice of immunotherapy in the treatment of cancer has improved the prognosis of many patients affected by various malignancies. The high expectations foreseen with immunotherapy have led to fast approvals despite the incomplete understanding of the toxicity profiles in the different organs, including the kidneys. The high prevalence of chronic kidney disease in cancer patients complicates the issue further and requires a better knowledge of the renal safety profile to ensure an optimal safe treatment. This review summarizes the present knowledge of renal adverse events secondary to immune checkpoint inhibitors and discusses their pathophysiology, clinical presentation and adequate management...
December 2016: Immunotherapy
Maya Habre, Samer Bassilios Habre, Hampig R Kourie
Immune checkpoint inhibitors (ICI) represent a new revolutionary weapon in the armamentarium of anti-cancer therapies. The side effects of these new agents represent a new challenge for oncologists; they are usually unpredictable and sometimes life threatening, if not managed rapidly and adequately. The most frequent side effects are the dermatologic, but they are usually low grade side effects and consequently easily manageable. Rash, pruritus and vitiligo are the most frequent dermatologic side effects. We aimed in this review to describe first all the dermatologic side effects of ICI according to the subtype of ICI and combination therapies in the clinical trials, then to report all the rare case reports dermatologic side effects, and finally to present the management algorithm of these side effects...
December 2016: Immunotherapy
Shunichiro Kuramitsu, Akane Yamamichi, Fumiharu Ohka, Kazuya Motomura, Masahito Hara, Atsushi Natsume
Patients with glioblastoma have a very poor prognosis. Adoptive cellular therapy (ACT) is defined as the collection of circulating or tumor-infiltrating lymphocytes, their selection, modification, expansion and activation, and their re-administration to patients in order to induce antitumor activity. Although various ACTs have been attempted, most failed to improve the outcome. Immune checkpoint blockade antibodies and T cell engineering with tumor-specific chimeric antigen receptors suggest the emergence of a new era of immunotherapy...
December 2016: Immunotherapy
Chuan Jin, Di Yu, Magnus Essand
Adoptive transfer of patient-derived T-cells engineered with a chimeric antigen receptor (CAR) targeting the pan-B-cell marker CD19 has led to complete remission in patients with B-cell leukemias while response rates are more modest for B-cell lymphomas. This can be attributed to the fact that the semi-solid structure of lymphomas impedes T-cell infiltration and that the immune suppressive microenvironment within these tumors dampens the effect of CAR T-cells. These obstacles are even more pronounced for solid tumors where dense and often highly immunosuppressive structures are found...
December 2016: Immunotherapy
Omar Abdel-Rahman
AIM: Pembrolizumab is a fully humanized anti-PD-1 agent currently approved for the treatment of advanced melanoma and pretreated non-small-cell lung cancer (NSCLC). OBJECTIVE: To assess the efficacy and safety of different dose schedules of pembrolizumab in the treatment of patients with advanced NSCLC and melanoma. Search method: MEDLINE database has been searched. Reference lists of original studies and review articles were checked for other related articles. SELECTION CRITERIA: Prospective clinical trials reporting the outcomes of more than one dose schedule of pembrolizumab in the treatment of advanced NSCLC and melanoma...
December 2016: Immunotherapy
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