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Journal for Immunotherapy of Cancer

Haris Zahoor, Pedro C Barata, Xuefei Jia, Allison Martin, Kimberly D Allman, Laura S Wood, Timothy D Gilligan, Petros Grivas, Moshe C Ornstein, Jorge A Garcia, Brian I Rini
BACKGROUND: Nivolumab is approved for the treatment of refractory metastatic renal cell carcinoma. Patterns and predictors of progressive disease (PD) on nivolumab, and outcomes in such patients are lacking. METHODS: A retrospective analysis of patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC) who received nivolumab at Cleveland Clinic (2015-2017) was performed. PD was defined per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or clinical progression as per treating physician...
October 17, 2018: Journal for Immunotherapy of Cancer
Yasuko Tada, Yosuke Togashi, Daisuke Kotani, Takeshi Kuwata, Eichi Sato, Akihito Kawazoe, Toshihiko Doi, Hisashi Wada, Hiroyoshi Nishikawa, Kohei Shitara
BACKGROUND: Several studies have established a correlation between the VEGF-VEGFR2 axis and an immunosuppressive microenvironment; this immunosuppression can be overcome by anti-angiogenic reagents, such as ramucirumab (RAM). However, little is known about the immunological impact of anti-angiogenic reagents within the tumor microenvironment in human clinical samples. This study aimed at investigating the effects of RAM on the tumor microenvironmental immune status in human cancers. METHODS: We prospectively enrolled 20 patients with advanced gastric cancer (GC) who received RAM-containing chemotherapy...
October 11, 2018: Journal for Immunotherapy of Cancer
Daniel H Johnson, Chrystia M Zobniw, Van A Trinh, Junsheng Ma, Roland L Bassett, Noha Abdel-Wahab, Jaime Anderson, Jennifer E Davis, Jocelyn Joseph, Marc Uemura, Ali Noman, Hamzah Abu-Sbeih, Cassian Yee, Rodabe Amaria, Sapna Patel, Hussein Tawbi, Isabella C Glitza, Michael A Davies, Michael K Wong, Scott Woodman, Wen-Jen Hwu, Patrick Hwu, Yinghong Wang, Adi Diab
BACKGROUND: Immune-related enterocolitis (irEC) is the most common serious complication from checkpoint inhibitors (CPIs). The current front-line treatment for irEC, high-dose corticosteroids (CS), have significant side effects and prolonged therapy may reduce CPI-anti-tumor activity. Early addition of TNF-α inhibitors such as infliximab (IFX) may expedite symptom resolution and shorten CS duration. Thus, we conducted the first retrospective study, to our knowledge, evaluating symptom resolution in patients with irEC treated with and without IFX...
October 11, 2018: Journal for Immunotherapy of Cancer
Fanny Chapelin, Christian M Capitini, Eric T Ahrens
Over the past two decades, immune cell therapy has emerged as a potent treatment for multiple cancers, first through groundbreaking leukemia therapy, and more recently, by tackling solid tumors. Developing successful therapeutic strategies using live cells could benefit from the ability to rapidly determine their in vivo biodistribution and persistence. Assaying cell biodistribution is unconventional compared to traditional small molecule drug pharmacokinetic readouts used in the pharmaceutical pipeline, yet this information is critical towards understanding putative therapeutic outcomes and modes of action...
October 11, 2018: Journal for Immunotherapy of Cancer
Kendall F Moseley, Jarushka Naidoo, Clifton O Bingham, Michael A Carducci, Patrick M Forde, Geoffrey T Gibney, Evan J Lipson, Ami A Shah, William H Sharfman, Laura C Cappelli
BACKGROUND: The use of immune checkpoint inhibitors is increasing in cancer therapy today. It is critical that treatment teams become familiar with the organ systems potentially impacted by immune-related adverse events associated with these drugs. Here, we report adverse skeletal effects of immunotherapy, a phenomenon not previously described. CASE PRESENTATIONS: In this retrospective case series, clinical, laboratory and imaging data were obtained in patients referred to endocrinology or rheumatology with new fractures (n = 3) or resorptive bone lesions (n = 3) that developed while on agents targeting PD-1, CTLA-4 or both...
October 11, 2018: Journal for Immunotherapy of Cancer
Maartje W Rohaan, Joost H van den Berg, Pia Kvistborg, John B A G Haanen
The treatment of metastatic melanoma patients with autologous tumor-infiltrating lymphocytes (TIL) shows robust, reproducible, clinical responses in clinical trials executed in several specialized centers over the world. Even in the era of targeted therapy and immune checkpoint inhibition, TIL therapy can be an additional and clinically relevant treatment line. This review provides an overview of the clinical experiences with TIL therapy thus far, including lymphodepleting regimens, the use of interleukin-2 (IL-2) and the associated toxicity...
October 3, 2018: Journal for Immunotherapy of Cancer
Bin Zhao, Hong Zhao, Jiaxin Zhao
BACKGROUND: Nivolumab, an immune checkpoint inhibitor, has revolutionized the treatment of many cancers. Due to its novel mechanisms of action, nivolumab induces a distinct profile of adverse events. Currently, the incidence and risk of developing serious adverse events (SAEs) or fatal adverse events (FAEs) following nivolumab administration are unclear. METHODS: We conducted a systematic search for phase 2 and phase 3 nivolumab trials in PubMed and Embase from inception to June 2018...
October 3, 2018: Journal for Immunotherapy of Cancer
Jingjing Duan, Yongwei Xie, Lijuan Qu, Lingxiong Wang, Shunkai Zhou, Yu Wang, Zhongyi Fan, Shengsheng Yang, Shunchang Jiao
BACKGROUND: Immunoscore, as a prognostic tool defined to quantify in situ immune cell infiltrates, appears to be superior to the TNM staging system. In esophageal squamous cell carcinoma (ESCC), no immunoscore has been established; however, in situ tumor immunology is recognized as highly important. Our study aimed to construct a comprehensive immunoprofile for ESCC. METHODS: The infiltration of four immune cell types (CD8+/CD4+/Foxp3+/CD33+ cells), the expression of both inhibitory (PD-1/PD-L1/Tim-3/LAG-3) and stimulatory checkpoints (OX-40/ICOS), and IDO1 were evaluated by IHC staining and multi-color immunofluorescence in two independent cohorts (95 patients in the primary cohort and 55 patients in the validation cohort)...
October 3, 2018: Journal for Immunotherapy of Cancer
Nathan D Pennock, Holly A Martinson, Qiuchen Guo, Courtney B Betts, Sonali Jindal, Takahiro Tsujikawa, Lisa M Coussens, Virginia F Borges, Pepper Schedin
BACKGROUND: Women diagnosed with breast cancer within 5 years postpartum (PPBC) have poorer prognosis than age matched nulliparous women, even after controlling for clinical variables known to impact disease outcomes. Through rodent modeling, the poor prognosis of PPBC has been attributed to physiologic mammary gland involution, which shapes a tumor promotional microenvironment through induction of wound-healing-like programs including myeloid cell recruitment. Previous studies utilizing immune compromised mice have shown that blocking prostaglandin synthesis reduces PPBC tumor progression in a tumor cell extrinsic manner...
October 1, 2018: Journal for Immunotherapy of Cancer
Michael Lattanzi, Fang-Ming Deng, Luis A Chiriboga, Alisa N Femia, Shane A Meehan, Gopa Iyer, Martin H Voss, Yuliya Sundatova, William C Huang, Arjun V Balar
BACKGROUND: Malignant angiomyolipoma is an uncommon tumor of the class of perivasciular epithelioid cell neoplasms (PEComas). These tumors are characteristically driven by deleterious mutations in the tumor suppressors TSC1 and TSC2, whose gene products typically act to inhibit mTOR. There are several cases of malignant angiomyolipoma which exhibit transient responses to mTOR inhibitors, forming the basis of current practice guidelines in malignant PEComa. However the tumors ultimately acquire resistance, and there is no well-established second-line option...
October 1, 2018: Journal for Immunotherapy of Cancer
Nicolas A Giraldo, Peter Nguyen, Elizabeth L Engle, Genevieve J Kaunitz, Tricia R Cottrell, Sneha Berry, Benjamin Green, Abha Soni, Jonathan D Cuda, Julie E Stein, Joel C Sunshine, Farah Succaria, Haiying Xu, Aleksandra Ogurtsova, Ludmila Danilova, Candice D Church, Natalie J Miller, Steve Fling, Lisa Lundgren, Nirasha Ramchurren, Jennifer H Yearley, Evan J Lipson, Mac Cheever, Robert A Anders, Paul T Nghiem, Suzanne L Topalian, Janis M Taube
BACKGROUND: We recently reported a 56% objective response rate in patients with advanced Merkel cell carcinoma (MCC) receiving pembrolizumab. However, a biomarker predicting clinical response was not identified. METHODS: Pretreatment FFPE tumor specimens (n = 26) were stained for CD8, PD-L1, and PD-1 by immunohistochemistry/immunofluorescence (IHC/IF), and the density and distribution of positive cells was quantified to determine the associations with anti-PD-1 response...
October 1, 2018: Journal for Immunotherapy of Cancer
Javier Rodriguez, Eduardo Castañón, Jose Luis Perez-Gracia, Inmaculada Rodriguez, Antonio Viudez, Carlos Alfaro, Carmen Oñate, Guiomar Perez, Fernando Rotellar, Susana Inogés, Ascensión López-Diaz de Cerio, Leyre Resano, Mariano Ponz-Sarvise, Maria E Rodriguez-Ruiz, Ana Chopitea, Ruth Vera, Ignacio Melero
Surgically resectable synchronic and metachronic liver metastases of colon cancer have high risk of relapse in spite of standard-of-care neoadjuvant and adjuvant chemotherapy regimens. Dendritic cell vaccines loaded with autologous tumor lysates were tested for their potential to avoid or delay disease relapses (NCT01348256). Patients with surgically amenable liver metastasis of colon adenocarcinoma (n = 19) were included and underwent neoadjuvant chemotherapy, surgery and adjuvant chemotherapy. Fifteen patients with disease-free resection margins were randomized 1:1 to receive two courses of four daily doses of dendritic cell intradermal vaccinations versus observation...
September 29, 2018: Journal for Immunotherapy of Cancer
Hamzah Abu-Sbeih, Faisal S Ali, Wenyi Luo, Wei Qiao, Gottumukkala S Raju, Yinghong Wang
BACKGROUND: Immune checkpoint inhibitors (ICPI) are efficacious treatments for advanced malignancies but can result in immune mediated diarrhea and colitis (IDC). Currently, the guidelines for the treatment of IDC depend only on clinical symptoms. Endoscopic and histologic features of such adverse events are not well studied in a manner that can help to gauge treatment plans. We aimed to characterize endoscopic and histologic features of IDC and to assess their association with clinical outcomes...
September 25, 2018: Journal for Immunotherapy of Cancer
Benjamin O Tschumi, Nina Dumauthioz, Bastien Marti, Lianjun Zhang, Evripidis Lanitis, Melita Irving, Pascal Schneider, Jean-Pierre Mach, George Coukos, Pedro Romero, Alena Donda
After publication of this article [1], it was noticed that 3 authors were missed from the author list.
September 25, 2018: Journal for Immunotherapy of Cancer
Ben Tran, Richard D Carvajal, Aurelien Marabelle, Sandip Pravin Patel, Patricia M LoRusso, Erik Rasmussen, Gloria Juan, Vijay V Upreti, Courtney Beers, Gataree Ngarmchamnanrith, Patrick Schöffski
BACKGROUND: This open-label, first-in-human, phase 1 study evaluated the safety, pharmacokinetics, pharmacodynamics, and maximum tolerated dose (MTD) of AMG 228, an agonistic human IgG1 monoclonal antibody targeting glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR), in patients with refractory advanced solid tumors. METHODS: AMG 228 was administered intravenously every 3 weeks (Q3W). Dose escalation was in two stages: single-patient cohorts (3, 9, 30, and 90 mg), followed by "rolling six" design (n = 2-6; 180, 360, 600, 900, and 1200 mg)...
September 25, 2018: Journal for Immunotherapy of Cancer
Michael J Wagner, Robert W Ricciotti, Jose Mantilla, Elizabeth T Loggers, Seth M Pollack, Lee D Cranmer
BACKGROUND: Chondrosarcoma is one of the most common malignant bone tumors in adults. Conventional chondrosarcoma represents around 85% of all chondrosarcomas and is notoriously difficult to treat with chemotherapy. CASE PRESENTATION: We describe a 67-year-old man with metastatic conventional chondrosarcoma who was treated with nivolumab. Treatment was discontinued after restaging showed increased tumor burden, which later proved to be pseudoprogression. The patient restarted nivolumab and continues to have a near complete response...
September 25, 2018: Journal for Immunotherapy of Cancer
Jason M Redman, Seth M Steinberg, James L Gulley
Advances in immunotherapy utilizing immune checkpoint inhibitors (ICIs) have transformed the treatment landscapes of several malignancies in recent years. Oncologists are now tasked with extending these benefits to a greater number of patients and tumor types. Metastatic castration-resistant prostate cancer (mCRPC) infrequently responds to ICIs, while the cellular vaccine approved for mCRPC, sipuleucel-T, provides a 4-month survival benefit but does not produce clinical responses as monotherapy. However, many novel and generally well-tolerated immune oncology agents with potential for immune synergy and/or additive effects are undergoing clinical development...
September 18, 2018: Journal for Immunotherapy of Cancer
Philip Friedlander, Kevin Wood, Karl Wassmann, Alan M Christenfeld, Nina Bhardwaj, William K Oh
BACKGROUND: Anti-CTLA-4 immune checkpoint blockade is associated with immune-related adverse events (irAEs). Grade 3-4 diarrhea/colitis is the most frequent irAE requiring treatment discontinuation. Predicting high-risk diarrhea/colitis patients may facilitate early intervention, limit irAE severity, and extend treatment duration. No biomarkers currently predict for anti-CTLA-4 immunotherapy related severe diarrhea. METHODS: Whole-blood was collected pre-treatment and 30 days post-treatment initiation from patients with stage III or IV unresectable melanoma who received 15 mg/kg tremelimumab at 90 day intervals in two clinical trials...
September 18, 2018: Journal for Immunotherapy of Cancer
Johannes C Melms, Rohit Thummalapalli, Kristin Shaw, Huihui Ye, Leo Tsai, Rupal S Bhatt, Benjamin Izar
The development of a new lesion in a patient with a complete remission to anti-PD-1 therapy is highly concerning for a drug resistant escape lesion. Here, we present a case of a 62-year-old patient with chemotherapy-resistant metastatic urothelial cancer who had a complete remission to pembrolizumab. The patient's disease burden tracked closely to serum levels of alpha-fetoprotein (AFP) expressed by the tumor and served as an accurate tumor marker. Surveillance imaging revealed a solitary growing pulmonary nodule mimicking an escape lesion in the absence of an increase in AFP levels...
September 12, 2018: Journal for Immunotherapy of Cancer
Guozhu Xie, Tan Cheng, Jie Lin, Lanfang Zhang, Jieling Zheng, Ying Liu, Guobo Xie, Baiyao Wang, Yawei Yuan
BACKGROUND: Current checkpoint immunotherapy has shown potential to control cancer by restoring or activating the immune system. Nevertheless, multiple mechanisms are involved in immunotherapy resistance which limits the clinical benefit of checkpoint inhibitors. An immunosuppressive microenvironment is an important factor mediating the original resistance of tumors to immunotherapy. A previous report by our group has demonstrated that local angiotensin II (AngII) predominantly exists in a tumor hypoxic microenvironment where hypoxic tumour cells produced AngII by a hypoxia-lactate-chymase-dependent mechanism...
September 12, 2018: Journal for Immunotherapy of Cancer
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