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https://www.readbyqxmd.com/read/29443657/il-2-and-beyond-in-cancer-immunotherapy
#1
John M Wrangle, Alicia Patterson, C Bryce Johnson, Daniel J Neitzke, Shikhar Mehrotra, Chadrick E Denlinger, Chrystal M Paulos, Zihai Li, David J Cole, Mark P Rubinstein
The development of the T- and natural killer (NK) cell growth factor IL-2 has been a sentinel force ushering in the era of immunotherapy in cancer. With the advent of clinical grade recombinant IL-2 in the mid-1980s, oncologists could for the first time directly manipulate lymphocyte populations with systemic therapy. By itself, recombinant IL-2 can induce clinical responses in up to 15% of patients with metastatic cancer or renal cell carcinoma. When administered with adoptively transferred tumor-reactive lymphocytes, IL-2 promotes T cell engraftment and response rates of up to 50% in metastatic melanoma patients...
February 2018: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29442540/management-of-immune-related-adverse-events-in-patients-treated-with-immune-checkpoint-inhibitor-therapy-american-society-of-clinical-oncology-clinical-practice-guideline
#2
Julie R Brahmer, Christina Lacchetti, Bryan J Schneider, Michael B Atkins, Kelly J Brassil, Jeffrey M Caterino, Ian Chau, Marc S Ernstoff, Jennifer M Gardner, Pamela Ginex, Sigrun Hallmeyer, Jennifer Holter Chakrabarty, Natasha B Leighl, Jennifer S Mammen, David F McDermott, Aung Naing, Loretta J Nastoupil, Tanyanika Phillips, Laura D Porter, Igor Puzanov, Cristina A Reichner, Bianca D Santomasso, Carole Seigel, Alexander Spira, Maria E Suarez-Almazor, Yinghong Wang, Jeffrey S Weber, Jedd D Wolchok, John A Thompson
Purpose To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapy. Methods A multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline. Guideline development involved a systematic review of the literature and an informal consensus process...
February 14, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29441454/chemotherapy-and-immunotherapy-for-recurrent-and-metastatic-head-and-neck-cancer-a-systematic-review
#3
REVIEW
Alessandro Guidi, Carla Codecà, Daris Ferrari
Head and neck cancer (HNC) is a fatal malignancy with an overall long-term survival of about 50% for all stages. The diagnosis is not rarely delayed, and the majority of patients present with loco-regionally advanced disease. The rate of second primary tumors after a diagnosis of HNC is about 3-7% per year, the highest rate among solid tumors. Currently, a single-modality or a combination of surgery, radiotherapy and chemotherapy (CHT), is the standard treatment for stage III-IV HNC. For the recurrent/metastatic setting, in the last 40 years great efforts have been made in order to develop a more effective CHT regimen, from the use of methotrexate alone, to the combination of cisplatin (CDDP) and 5-fluorouracile (5FU) or paclitaxel...
February 13, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29441072/fatal-necrotizing-encephalopathy-after-treatment-with-nivolumab-for-squamous-non-small-cell-lung-cancer-case-report-and-review-of-the-literature
#4
Markus Leitinger, Mihael V Varosanec, Slaven Pikija, Romana E Wass, Dave Bandke, Serge Weis, Michael Studnicka, Susanne Grinzinger, Mark R McCoy, Larissa Hauer, Johann Sellner
Immune checkpoint inhibitors are antibodies, which enhance cellular and humoral immune responses and are approved for the treatment of various tumors. Immune-related adverse events (irAE) involving different organs and systems are, however, among the side-effects. Recent reports of severe persistent neurological deficits and even fatal cases underpin the need for better understanding of the exact pathomechanisms of central nervous system (CNS) toxicity. To our knowledge, we report the first biopsy-proven case of fatal necrotizing encephalopathy after treatment with nivolumab...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29439857/axitinib-in-combination-with-pembrolizumab-in-patients-with-advanced-renal-cell-cancer-a-non-randomised-open-label-dose-finding-and-dose-expansion-phase-1b-trial
#5
Michael B Atkins, Elizabeth R Plimack, Igor Puzanov, Mayer N Fishman, David F McDermott, Daniel C Cho, Ulka Vaishampayan, Saby George, Thomas E Olencki, Jamal C Tarazi, Brad Rosbrook, Kathrine C Fernandez, Mariajose Lechuga, Toni K Choueiri
BACKGROUND: Previous studies combining PD-1 checkpoint inhibitors with tyrosine kinase inhibitors of the VEGF pathway have been characterised by excess toxicity, precluding further development. We hypothesised that axitinib, a more selective VEGF inhibitor than others previously tested, could be combined safely with pembrolizumab (anti-PD-1) and yield antitumour activity in patients with treatment-naive advanced renal cell carcinoma. METHODS: In this ongoing, open-label, phase 1b study, which was done at ten centres in the USA, we enrolled patients aged 18 years or older who had advanced renal cell carcinoma (predominantly clear cell subtype) with their primary tumour resected, and at least one measureable lesion, Eastern Cooperative Oncology Group performance status 0-1, controlled hypertension, and no previous systemic therapy for renal cell carcinoma...
February 9, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29437773/autoimmune-fasciitis-triggered-by-the-anti-programmed-cell-death-1-monoclonal-antibody-nivolumab
#6
Matthew Js Parker, Mark E Roberts, Paul C Lorigan, Daniel G du Plessis, Hector Chinoy
A 43-year-old woman with a history of recently diagnosed metastatic melanoma was commenced on systemic therapy with nivolumab, an anti-programmed cell death-1 monoclonal antibody and one of an increasing group of the so-called 'immune checkpoint inhibitors'. She experienced a dramatic complete response within 6 months of initiation. However, in addition to developing incident autoimmune hypothyroidism, she also developed progressive fatigue, proximal weakness, myalgia and dysphagia. Initial investigations with blood tests, electrophysiology and a muscle biopsy were non-specific or normal...
February 8, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29437040/durable-clinical-benefit-in-metastatic-renal-cell-carcinoma-patients-who-discontinue-pd-1-pd-l1-therapy-for-immune-related-adverse-events-iraes
#7
Dylan J Martini, Lana Hamieh, Rana R McKay, Lauren C Harshman, Raphael Brandao, Craig K Norton, John A Steinharter, Katherine M Krajewski, Xin Gao, Fabio A Schutz, Bradley McGregor, Dominick Bosse, Aly-Khan Lalani, Guillermo de Velasco, M Dror Michaelson, David F McDermott, Toni K Choueiri
The current standard of care for treatment of metastatic renal cell carcinoma (mRCC) patients is PD-1/PD-L1 inhibitors until progression or toxicity. Here we characterize the clinical outcomes for 19 mRCC patients who experienced an initial clinical response (any degree of tumor shrinkage), but after immune-related adverse events (irAEs) discontinued all systemic therapy. Clinical baseline characteristics, outcomes, and survival data were collected. The primary end-point was time to progression from the date of treatment cessation (TTP)...
February 1, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29436395/myeloid-targeted-immunotherapies-act-in-synergy-to-induce-inflammation-and-antitumor-immunity
#8
Curtis J Perry, Andrés R Muñoz-Rojas, Katrina M Meeth, Laura N Kellman, Robert A Amezquita, Durga Thakral, Victor Y Du, Jake Xiao Wang, William Damsky, Alexandra L Kuhlmann, Joel W Sher, Marcus Bosenberg, Kathryn Miller-Jensen, Susan M Kaech
Eliciting effective antitumor immune responses in patients who fail checkpoint inhibitor therapy is a critical challenge in cancer immunotherapy, and in such patients, tumor-associated myeloid cells and macrophages (TAMs) are promising therapeutic targets. We demonstrate in an autochthonous, poorly immunogenic mouse model of melanoma that combination therapy with an agonistic anti-CD40 mAb and CSF-1R inhibitor potently suppressed tumor growth. Microwell assays to measure multiplex protein secretion by single cells identified that untreated tumors have distinct TAM subpopulations secreting MMP9 or cosecreting CCL17/22, characteristic of an M2-like state...
February 7, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29436178/microsatellite-instability-status-determined-by-next-generation-sequencing-and-compared-with-pd-l1-and-tumor-mutational-burden-in-11-348-patients
#9
Ari Vanderwalde, David Spetzler, Nianqing Xiao, Zoran Gatalica, John Marshall
Microsatellite instability (MSI) testing identifies patients who may benefit from immune checkpoint inhibitors. We developed an MSI assay that uses data from a commercially available next-generation sequencing (NGS) panel to determine MSI status. The assay is applicable across cancer types and does not require matched samples from normal tissue. Here, we describe the MSI-NGS method and explore the relationship of MSI with tumor mutational burden (TMB) and PD-L1. MSI examined by PCR fragment analysis and NGS was compared for 2189 matched cases...
February 13, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29435437/improvement-of-antitumor-therapies-based-on-vaccines-and-immune-checkpoint-inhibitors-by-counteracting-tumor-immunostimulation
#10
Paula Chiarella, Mónica Vermeulen, Daniela R Montagna, Pablo Vallecorsa, Ariel Ramiro Strazza, Roberto P Meiss, Oscar D Bustuoabad, Raúl A Ruggiero, Richmond T Prehn
Immune-checkpoint inhibitors and antitumor vaccines may produce both tumor-inhibitory and tumor-stimulatory effects on growing tumors depending on the stage of tumor growth at which treatment is initiated. These paradoxical results are not necessarily incompatible with current tumor immunology but they might better be explained assuming the involvement of the phenomenon of tumor immunostimulation. This phenomenon was originally postulated on the basis that the immune response (IR) evoked in Winn tests by strong chemical murine tumors was not linear but biphasic, with strong IR producing inhibition and weak IR inducing stimulation of tumor growth...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29435295/identification-of-candidate-responders-for-anti-pd-l1-pd-1-immunotherapy-rova-t-therapy-or-ezh2-inhibitory-therapy-in-small-cell-lung-cancer
#11
Motonobu Saito, Katsuharu Saito, Kouya Shiraishi, Daichi Maeda, Hiroyuki Suzuki, Yoshihiro Minamiya, Koji Kono, Takashi Kohno, Akiteru Goto
A useful candidate for small-cell lung cancer (SCLC) therapy is immune checkpoint blockade therapy targeting programmed death-1 (PD-1) and its ligand, PD-L1. Furthermore, rovalpituzumab tesirine (Rova-T), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate, and enhancer of zeste homologue 2 (EZH2) inhibitor are expected to be the first targeted therapy for SCLC. The aim of the present study was to evaluate PD-L1, DLL3 and EZH2 expression in SCLCs to find a candidate responder to those therapies. Immunohistochemical (IHC) staining for PD-L1, DLL3 and EZH2 was performed in 20 patients with SCLC and the clinicopathological characteristics and IHC staining intensity were compared...
February 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29435193/targeted-drugs-for-systemic-therapy-of-lung-cancer-with-brain-metastases
#12
REVIEW
Ya-Wen Sun, Jian Xu, Jun Zhou, Wen-Juan Liu
Brain metastases are very common in lung cancer patients. The condition of these patients is complicated and difficult to treat, and adverse reactions following treatment can affect the nervous system, which severely reduces quality of life. Lung cancers are categorized as small cell lung cancers and non-small cell lung cancers. Patients with brain metastasis of small cell lung cancers are generally treated with brain radiotherapy and systemic chemotherapy, but stage III/IV patients with brain metastasis of non-small cell lung cancers are generally not responsive to radiotherapy or chemotherapy...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435038/high-expression-of-carcinoembryonic-antigen-and-telomerase-reverse-transcriptase-in-circulating-tumor-cells-is-associated-with-poor-clinical-response-to-the-immune-checkpoint-inhibitor-nivolumab
#13
Halin Bao, Tuya Bai, Koji Takata, Takehiko Yokobori, Takashi Ohnaga, Takeshi Hisada, Toshitaka Maeno, Pinjie Bao, Tomonori Yoshida, Yuji Kumakura, Hiroaki Honjo, Makoto Sakai, Makoto Sohda, Minoru Fukuchi, Bolag Altan, Tadashi Handa, Munenori Ide, Tatsuya Miyazaki, Kyoichi Ogata, Tetsunari Oyama, Kimihiro Shimizu, Akira Mogi, Takayuki Asao, Ken Shirabe, Hiroyuki Kuwano, Kyoichi Kaira
The present study aimed to enrich circulating tumor cells (CTCs) from blood samples using a new size-sorting CTC chip. The present study also set out to identify a blood sensitivity marker for the immune checkpoint inhibitor nivolumab in patients with advanced, pre-treatment lung cancer. The CTC sorting efficacy of the chip was investigated and the large cell fraction of blood samples from 15 patients with pre-treatment lung cancer who were later administered nivolumab were purified. The expression levels of carcinoembryonic antigen (CEA), human Telomerase Reverse Transcriptase (hTERT), cytokeratin19 (CK19), and programmed death ligand-1 (PD-L1) were investigated to clarify the association between these CTC markers and the clinical response to nivolumab...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434366/potentiating-prostate-cancer-immunotherapy-with-oncolytic-viruses
#14
REVIEW
Patrick Lee, Shashi Gujar
The clinical effectiveness of immunotherapies for prostate cancer remains subpar compared with that for other cancers. The goal of most immunotherapies is the activation of immune effectors, such as T cells and natural killer cells, as the presence of these activated mediators positively correlates with patient outcomes. Clinical evidence shows that prostate cancer is immunogenic, accessible to the immune system, and can be targeted by antitumour immune responses. However, owing to the detrimental effects of prostate-cancer-associated immunosuppression, even the newest immunotherapeutic approaches fail to initiate the clinically desired antitumour immune reaction...
February 13, 2018: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29434333/improving-immunotherapy-outcomes-with-anti-angiogenic-treatments-and-vice-versa
#15
REVIEW
Kabir A Khan, Robert S Kerbel
Immunotherapies have revolutionized medical oncology following the remarkable and, in some cases, unprecedented outcomes observed in certain groups of patients with cancer. Combination with other therapeutic modalities, including anti-angiogenic agents, is one of the many strategies currently under investigation to improve the response rates and duration of immunotherapies. Such a strategy might seem counterintuitive given that anti-angiogenic agents can increase tumour hypoxia and reduce the number of blood vessels within tumours...
February 13, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29433571/granulomatous-sarcoid-like-lesions-associated-with-checkpoint-inhibitors-a-marker-of-therapy-response-in-a-subset-of-melanoma-patients
#16
Michael T Tetzlaff, Kelly C Nelson, Adi Diab, Gregg A Staerkel, Priyadharsini Nagarajan, Carlos A Torres-Cabala, Beth A Chasen, Jennifer A Wargo, Victor G Prieto, Rodabe N Amaria, Jonathan L Curry
BACKGROUND: Immune checkpoint therapy has dramatically changed the landscape of cancer therapy, providing an efficacious and durable therapeutic option for patients with advanced-stage disease. However, dermatologic toxicities are a well-recognized side effect in patients receiving this therapy. A spectrum of immune related adverse events (irAEs) involving the skin can occur and include immunobullous disorders, lichenoid dermatitis, and vitiligo. Granulomatous/sarcoid-like lesions are now being recognized with the current class of checkpoint inhibitors (CPIs) that involve the dermis, the subcutaneous tissue (panniculitis), and lymph nodes...
February 12, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29433557/metastatic-uveal-melanoma-showing-durable-response-to-anti-ctla-4-and-anti-pd-1-combination-therapy-after-experiencing-progression-on-anti-pd-1-therapy-alone
#17
Muhammad Zubair Afzal, Rodwell Mabaera, Keisuke Shirai
BACKGROUND: Uveal melanoma accounts for 85% of the ocular melanomas and has an increased risk of hematogenous spread, most commonly to the liver. After curative intent therapy like surgery and radiation, fifty percent of patients present with distant metastasis. Metastatic uveal melanoma (MUM) does not harbor typically targetable mutations, e.g., BRAF as in cutaneous melanoma. As a result, there is no proven therapy for MUM. Various chemotherapy and immunotherapy regimens have been tried and only partial response (PR) is the best that has been achieved in most of the cases...
February 12, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29432557/epigenetic-modifiers-as-new-immunomodulatory-therapies-in-solid-tumours
#18
S Aspeslagh, D Morel, J-C Soria, S Postel-Vinay
Background: Immune therapies have revolutionized cancer treatment over the last few years by allowing improvements in overall survival. However, the majority of patients is still primary or secondary resistant to such therapies, and enhancing sensitivity to immune therapies is therefore crucial to improve patient outcome. Several recent lines of evidence suggest that epigenetic modifiers have intrinsic immunomodulatory properties, which could be of therapeutic interest. Material and Methods: We reviewed preclinical evidence and clinical studies which describe or exploit immunomodulatory properties of epigenetic agents...
February 7, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29432222/immunotherapy-for-recurrent-metastatic-head-and-neck-cancer
#19
Salvatore Alfieri, Stefano Cavalieri, Lisa Licitra
PURPOSE OF REVIEW: In the last decade, after cetuximab (anti-epidermal growth factor receptor), none of the novel investigated compounds has demonstrated benefit in head and neck squamous cell cancers (HNSCC), both in advanced and curative settings. Therefore, prognosis of recurrent/metastatic (R/M) HNSCC patients remains dismal, especially in platinum-refractory cohort. In the last few years, a new important class of drugs has affirmed its role. HNSCC, even if less 'immunogenic' than other malignancies (e...
February 8, 2018: Current Opinion in Otolaryngology & Head and Neck Surgery
https://www.readbyqxmd.com/read/29431673/a-critical-need-for-better-cancer-immunotherapy-models-are-organotypic-tumor-spheroid-cultures-the-answer
#20
Justin M Balko, Jeffrey A Sosman
Immunotherapy has transformed the therapeutic landscape of cancer, but the preclinical evaluation of combination approaches that will deepen and broaden its clinical benefit has lagged far behind due to the lack of expedient and easily accessible ex vivo human systems. In this issue, Jenkins and colleagues and Deng and colleagues report the use of organotypic cultures of tumors derived from mice and humans containing both tumor cells and cells from their local immune microenvironment to recapitulate the in vivo use of immune checkpoint inhibitors and extend the application of this system to therapeutic combinations of immune checkpoint blockade and molecularly targeted agents...
February 2018: Cancer Discovery
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