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Journal for Immunotherapy of Cancer

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https://www.readbyqxmd.com/read/29162153/managing-toxicities-associated-with-immune-checkpoint-inhibitors-consensus-recommendations-from-the-society-for-immunotherapy-of-cancer-sitc-toxicity-management-working-group
#1
I Puzanov, A Diab, K Abdallah, C O Bingham, C Brogdon, R Dadu, L Hamad, S Kim, M E Lacouture, N R LeBoeuf, D Lenihan, C Onofrei, V Shannon, R Sharma, A W Silk, D Skondra, M E Suarez-Almazor, Y Wang, K Wiley, H L Kaufman, M S Ernstoff
Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs' therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29157311/peripheral-and-local-predictive-immune-signatures-identified-in-a-phase-ii-trial-of-ipilimumab-with-carboplatin-paclitaxel-in-unresectable-stage-iii-or-stage-iv-melanoma
#2
Rahima Jamal, Réjean Lapointe, Eftihia Cocolakis, Paméla Thébault, Shirin Kazemi, Jennifer E Friedmann, Jeanne Dionne, Jean-François Cailhier, Karl Bélanger, Jean-Pierre Ayoub, Huy Le, Caroline Lambert, Jida El-Hajjar, Léon C van Kempen, Alan Spatz, Wilson H Miller
BACKGROUND: Checkpoint blockade with ipilimumab provides long-term survival to a significant proportion of patients with metastatic melanoma. New approaches to increase survival and to predict which patients will benefit from treatment are needed. This phase II trial combined ipilimumab with carboplatin/paclitaxel (CP) to assess its safety, efficacy, and to search for peripheral and tumor-based predictive biomarkers. METHODS: Thirty patients with untreated unresectable/metastatic melanoma were treated with ipilimumab and CP...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29157306/a-pilot-study-of-the-immunogenicity-of-a-9-peptide-breast-cancer-vaccine-plus-poly-iclc-in-early-stage-breast-cancer
#3
Patrick M Dillon, Gina R Petroni, Mark E Smolkin, David R Brenin, Kimberly A Chianese-Bullock, Kelly T Smith, Walter C Olson, Ibrahim S Fanous, Carmel J Nail, Christiana M Brenin, Emily H Hall, Craig L Slingluff
BACKGROUND: Breast cancer remains a leading cause of cancer death worldwide. There is evidence that immunotherapy may play a role in the eradication of residual disease. Peptide vaccines for immunotherapy are capable of durable immune memory, but vaccines alone have shown sparse clinical activity against breast cancer to date. Toll-like receptor (TLR) agonists and helper peptides are excellent adjuvants for vaccine immunotherapy and they are examined in this human clinical trial. METHODS: A vaccine consisting of 9 MHC class I-restricted breast cancer-associated peptides (from MAGE-A1, -A3, and -A10, CEA, NY-ESO-1, and HER2 proteins) was combined with a TLR3 agonist, poly-ICLC, along with a helper peptide derived from tetanus toxoid...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29157300/prospects-for-combined-use-of-oncolytic-viruses-and-car-t-cells
#4
REVIEW
Adam Ajina, John Maher
With the approval of talimogene laherparepvec (T-VEC) for inoperable locally advanced or metastatic malignant melanoma in the USA and Europe, oncolytic virotherapy is now emerging as a viable therapeutic option for cancer patients. In parallel, following the favourable results of several clinical trials, adoptive cell transfer using chimeric antigen receptor (CAR)-redirected T-cells is anticipated to enter routine clinical practice for the management of chemotherapy-refractory B-cell malignancies. However, CAR T-cell therapy for patients with advanced solid tumours has proved far less successful...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29157298/impressive-response-to-immunotherapy-in-a-metastatic-gastric-cancer-patient-could-somatic-copy-number-alterations-help-patient-selection
#5
Gustavo Dos Santos Fernandes, Daniel da Motta Girardi, Luiza Dib Batista Bugiato Faria, João Paulo Giacomini Bernardes, Renata de Almeida Coudry
BACKGROUND: Metastatic gastric cancer (GC) is an incurable and aggressive disease with a poor prognosis. Immunotherapy is an attractive approach for treating patients with cancer, and studies using immunotherapy have shown promising results in melanoma, kidney and non-small cell lung cancers, among others. CASE PRESENTATION: We present a case of a 50-year-old woman with metastatic GC whose cancer had progressed after first-line chemotherapy and who received pembrolizumab as an experimental treatment...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29157297/smoldering-myocarditis-following-immune-checkpoint-blockade
#6
Timothy G Norwood, Brian C Westbrook, Douglas B Johnson, Silvio H Litovsky, Nina L Terry, Svetlana B McKee, Alan S Gertler, Javid J Moslehi, Robert M Conry
BACKGROUND: Severe myocarditis associated with electrical conduction abnormalities and occasionally heart failure has been well documented following treatment with immune checkpoint blockade with an estimated incidence of less than 1%. However, the incidence, early detection, and management of less severe immune-related myocarditis are unknown since most immunotherapy trials have not included routine cardiac monitoring. Herein, we provide the first description of subclinical or smoldering myocarditis with minimal signs and symptoms following immune checkpoint blockade with a single dose of ipilimumab and nivolumab...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29157296/biomarkers-for-immunotherapy-in-bladder-cancer-a-moving-target
#7
REVIEW
David H Aggen, Charles G Drake
Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30 years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis. Notably, the anti-PD-1 antibody pembrolizumab demonstrated improved OS relative to chemotherapy in a randomized phase III study for second line treatment of mUC; this level 1 evidence led to approval from the U...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29157295/single-cell-multiplexed-cytokine-profiling-of-cd19-car-t-cells-reveals-a-diverse-landscape-of-polyfunctional-antigen-specific-response
#8
Qiong Xue, Emily Bettini, Patrick Paczkowski, Colin Ng, Alaina Kaiser, Timothy McConnell, Olja Kodrasi, Máire F Quigley, James Heath, Rong Fan, Sean Mackay, Mark E Dudley, Sadik H Kassim, Jing Zhou
BACKGROUND: It remains challenging to characterize the functional attributes of chimeric antigen receptor (CAR)-engineered T cell product targeting CD19 related to potency and immunotoxicity ex vivo, despite promising in vivo efficacy in patients with B cell malignancies. METHODS: We employed a single-cell, 16-plex cytokine microfluidics device and new analysis techniques to evaluate the functional profile of CD19 CAR-T cells upon antigen-specific stimulation. CAR-T cells were manufactured from human PBMCs transfected with the lentivirus encoding the CD19-BB-z transgene and expanded with anti-CD3/anti-CD28 coated beads...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29157287/safety-in-treatment-of-hepatocellular-carcinoma-with-immune-checkpoint-inhibitors-as-compared-to-melanoma-and-non-small-cell-lung-cancer
#9
Zachary J Brown, Bernd Heinrich, Seth M Steinberg, Su Jong Yu, Tim F Greten
BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem worldwide with increasing incidence rates. As HCC traditionally occurs in chronically inflamed livers, this inflammation aids to drive oncogenesis and often renders these lesions to be immunogenic and therefore potential targets for immunotherapy. As patients with HCC generally have underlying liver dysfunction, we sought to determine if immune checkpoint inhibitors were safe to use in patients with HCC as compared to melanoma and non-small cell lung cancer (NSCLC) in terms of the gastrointestinal side effects of elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and diarrhea as well as patients who drop out of the study due to drug toxicity and death secondary to drug toxicity...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29110706/correction-to-genetic-engineering-of-human-nk-cells-to-express-cxcr2-improves-migration-to-renal-cell-carcinoma
#10
Veronika Kremer, Maarten A Ligtenberg, Rosa Zendehdel, Christina Seitz, Annet Duivenvoorden, Erik Wennerberg, Eugenia Colón, Ann-Helén Scherman-Plogell, Andreas Lundqvist
No abstract text is available yet for this article.
November 6, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29041991/neutrophil-lymphocyte-ratio-and-duration-of-prior-anti-angiogenic-therapy-as-biomarkers-in-metastatic-rcc-receiving-immune-checkpoint-inhibitor-therapy
#11
Ghayathri Jeyakumar, Seongho Kim, Naresh Bumma, Craig Landry, Cynthia Silski, Stacey Suisham, Brenda Dickow, Elisabeth Heath, Joseph Fontana, Ulka Vaishampayan
BACKGROUND: There is an unmet need to determine factors predictive of clinical benefit, to guide therapeutic sequencing and selection in metastatic RCC (mRCC). We evaluated clinical factors such as the neutrophil lymphocyte ratio (NLR) and duration of prior anti-vascular endothelial growth factor (VEGF) inhibitors, as predictors of response rate, progression free survival (PFS) and overall survival (OS) in mRCC patients treated with immune checkpoint inhibitor (ICI). METHODS: Regulatory approval was obtained...
October 17, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29037259/immuno-thermal-ablations-boosting-the-anticancer-immune-response
#12
REVIEW
Ryan Slovak, Johannes M Ludwig, Scott N Gettinger, Roy S Herbst, Hyun S Kim
The use of immunomodulation to treat malignancies has seen a recent explosion in interest. The therapeutic appeal of these treatments is far reaching, and many new applications continue to evolve. In particular, immune modulating drugs have the potential to enhance the systemic anticancer immune effects induced by locoregional thermal ablation. The immune responses induced by ablation monotherapy are well documented, but independently they tend to be incapable of evoking a robust antitumor response. By adding immunomodulators to traditional ablative techniques, several researchers have sought to amplify the induced immune response and trigger systemic antitumor activity...
October 17, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29037255/objective-measurement-and-clinical-significance-of-ido1-protein-in-hormone-receptor-positive-breast-cancer
#13
Daniel E Carvajal-Hausdorf, Nikita Mani, Vamsidhar Velcheti, Kurt A Schalper, David L Rimm
BACKGROUND: Immunostimulatory therapies targeting immune-suppressive pathways produce durable responses in advanced solid tumors. Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting oxidoreductase that catalyzes the degradation of tryptophan to kynurenine. IDO induces immune tolerance by downregulating CD8+ and effector CD4+ T cell responses. IDO1, the most active isoform, is expressed in diverse tumor types and can be targeted using small molecule inhibitors. We used an objective, in situ assay to measure IDO1 in a collection of hormone receptor-positive breast cancers (HR+ BC)...
October 17, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29037250/the-immune-system-in-cancer-metastasis-friend-or-foe
#14
REVIEW
Louise M E Janssen, Emma E Ramsay, Craig D Logsdon, Willem W Overwijk
Metastatic disease is the leading cause of death among cancer patients and involves a complex and inefficient process. Every step of the metastatic process can be rate limiting and is influenced by non-malignant host cells interacting with the tumor cell. Over a century ago, experiments first indicated a link between the immune system and metastasis. This phenomenon, called concomitant immunity, indicates that the primary tumor induces an immune response, which may not be sufficient to destroy the primary tumor, but prevents the growth of a secondary tumor or metastases...
October 17, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29037215/melanoma-brain-metastases-treated-with-stereotactic-radiosurgery-and-concurrent-pembrolizumab-display-marked-regression-efficacy-and-safety-of-combined-treatment
#15
Erik S Anderson, Michael A Postow, Jedd D Wolchok, Robert J Young, Åse Ballangrud, Timothy A Chan, Yoshiya Yamada, Kathryn Beal
BACKGROUND: Brain metastases are common in patients with metastatic melanoma. With increasing numbers of melanoma patients on anti-PD-1 therapy, we sought to evaluate the safety and initial response of brain metastases treated with concurrent pembrolizumab and radiation therapy. METHODS: From an institutional database, we retrospectively identified patients with melanoma brain metastases treated with radiation therapy (RT) who received concurrent pembrolizumab. Concurrent treatment was defined as RT during pembrolizumab administration period and up to 4 months after most recent pembrolizumab treatment...
October 17, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28962591/erratum-to-society-for-immunotherapy-of-cancer-consensus-statement-on-immunotherapy-for-the-treatment-of-bladder-carcinoma
#16
Ashish M Kamat, Joaquim Bellmunt, Matthew D Galsky, Badrinath R Konety, Donald L Lamm, David Langham, Cheryl T Lee, Matthew I Milowsky, Michael A O'Donnell, Peter H O'Donnell, Daniel P Petrylak, Padmanee Sharma, Eila C Skinner, Guru Sonpavde, John A Taylor, Prasanth Abraham, Jonathan E Rosenberg
No abstract text is available yet for this article.
September 28, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28923120/high-dose-interleukin-2-hd-il-2-for-advanced-melanoma-a-single-center-experience-from-the-university-of-pittsburgh-cancer-institute
#17
Diwakar Davar, Fei Ding, Melissa Saul, Cindy Sander, Ahmad A Tarhini, John M Kirkwood, Hussein A Tawbi
BACKGROUND: Durable remissions are observed in a fraction of metastatic melanoma patients treated with high-dose interleukin-2 (HD IL-2). Early studies reported overall (OR) and complete response (CR) rates of 16% and 8% respectively. Toxicity limited use to specialized centers with standardized protocols. We report on 243 patients treated at the University of Pittsburgh in a non-intensive care unit (ICU) oncology specialty setting. METHODS: Clinical and radiological data were collected on 243 patients treated between 1992 and 2015...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28923105/genetic-engineering-of-human-nk-cells-to-express-cxcr2-improves-migration-to-renal-cell-carcinoma
#18
Veronika Kremer, Maarten Ligtenberg, Rosa Zendehdel, Christina Seitz, Annet Duivenvoorden, Erik Wennerberg, Eugenia Colón, Ann-Helén Scherman-Plogell, Andreas Lundqvist
BACKGROUND: Adoptive natural killer (NK) cell transfer is being increasingly used as cancer treatment. However, clinical responses have so far been limited to patients with hematological malignancies. A potential limiting factor in patients with solid tumors is defective homing of the infused NK cells to the tumor site. Chemokines regulate the migration of leukocytes expressing corresponding chemokine receptors. Various solid tumors, including renal cell carcinoma (RCC), readily secrete ligands for the chemokine receptor CXCR2...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28923104/phase-1-study-of-intravenous-administration-of-the-chimeric-adenovirus-enadenotucirev-in-patients-undergoing-primary-tumor-resection
#19
Rocio Garcia-Carbonero, Ramon Salazar, Ignacio Duran, Ignacio Osman-Garcia, Luis Paz-Ares, Juan M Bozada, Valentina Boni, Christine Blanc, Len Seymour, John Beadle, Simon Alvis, Brian Champion, Emiliano Calvo, Kerry Fisher
BACKGROUND: Enadenotucirev (formerly ColoAd1) is a tumor-selective chimeric adenovirus with demonstrated preclinical activity. This phase 1 Mechanism of Action study assessed intravenous (IV) delivery of enadenotucirev in patients with resectable colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), urothelial cell cancer (UCC), and renal cell cancer (RCC) with a comparator intratumoral (IT) dosed CRC patient cohort. METHODS: Seventeen patients scheduled for primary tumor resection were enrolled...
September 19, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28923102/workshop-on-challenges-insights-and-future-directions-for-mouse-and-humanized-models-in-cancer-immunology-and-immunotherapy-a-report-from-the-associated-programs-of-the-2016-annual-meeting-for-the-society-for-immunotherapy-of-cancer
#20
Andrew Zloza, A Karolina Palucka, Lisa M Coussens, Philip J Gotwals, Mark B Headley, Elizabeth M Jaffee, Amanda W Lund, Arlene H Sharpe, Mario Sznol, Derek A Wainwright, Kwok-Kin Wong, Marcus W Bosenberg
Understanding how murine models can elucidate the mechanisms underlying antitumor immune responses and advance immune-based drug development is essential to advancing the field of cancer immunotherapy. The Society for Immunotherapy of Cancer (SITC) convened a workshop titled, "Challenges, Insights, and Future Directions for Mouse and Humanized Models in Cancer Immunology and Immunotherapy" as part of the SITC 31st Annual Meeting and Associated Programs on November 10, 2016 in National Harbor, MD. The workshop focused on key issues in optimizing models for cancer immunotherapy research, with discussions on the strengths and weaknesses of current models, approaches to improve the predictive value of mouse models, and advances in cancer modeling that are anticipated in the near future...
September 19, 2017: Journal for Immunotherapy of Cancer
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