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Journal of Immunotherapy

Yanfen Liu, Xinfeng Chen, Dao Wang, Hong Li, Jianmin Huang, Zhen Zhang, Yingjin Qiao, Hongling Zhang, Ying Zeng, Chao Tang, Shuangning Yang, Xiaochun Wan, Youhai H Chen, Yi Zhang
Cytokine release syndrome (CRS) remains to be a major adverse effect of chimeric antigen receptor T (CAR-T) cell therapy in B-cell acute lymphoblastic leukemia (B-ALL) and lymphoma. It was urgent to explore novel strategy for managing severe CRS. We conducted a clinical trial to assess the safety and efficacy of CD19-targeting CAR-T-cells in the treatment of relapsed and chemotherapy-refractory B-ALL and lymphoma. A 10-year-old boy with B-ALL who never achieved minimal residual disease (MRD) negative status after 5 courses of chemotherapy was enrolled into our study and received a total of 3...
September 6, 2018: Journal of Immunotherapy
Fang Zheng, Jianzhong Dang, Hongyu Zhang, Fangzhou Xu, Diandian Ba, Bingyu Zhang, Fanjun Cheng, Alfred E Chang, Max S Wicha, Qiao Li
Immune checkpoint inhibitors and monoclonal antibodies reinvigorate cancer immunotherapy. However, these immunotherapies only benefit a subset of patients. We previously reported that ALDH tumor cells were highly enriched for cancer stem cells (CSCs), and ALDH CSC lysate-pulsed dendritic cell (CSC-DC) vaccine was shown to induce CSC-specific cytotoxic T lymphocytes. In this study, we investigated the CSC targeting effect of the CSC-DC vaccine combined with a dual blockade of programmed death-ligand 1 and cytotoxic T-lymphocyte-associated protein (CTLA-4) in B16-F10 murine melanoma tumor model...
October 2018: Journal of Immunotherapy
Elaine Chang, Anita L Sabichi, Jennifer R Kramer, Christine Hartman, Kathryn E Royse, Donna L White, Niraj R Patel, Peter Richardson, Sarvari V Yellapragada, Jose M Garcia, Elizabeth Y Chiao
Nivolumab is a standard treatment option in several advanced malignancies, but safety and efficacy are still unknown in patients with human immunodeficiency virus (HIV) infection. We describe a case series of people living with HIV (PLWH) receiving nivolumab in the Veterans Health Administration (VA) and report responses and toxicities. We identified all PLWH who received nivolumab at any VA facility since 2000 in the Corporate Data Warehouse (CDW), which provides nationwide research access to VA electronic medical records...
October 2018: Journal of Immunotherapy
Min Dai, Ingegerd Hellstrom, Yuen Y Yip, Hans Olov Sjögren, Karl Erik Hellstrom
While immunomodulatory monoclonal antibodies (mAbs) have therapeutic efficacy against many tumors, few patients are cured. Attempting to improve their therapeutic efficacy we have applied the TC1 mouse lung carcinoma model and injected established subcutaneous tumors intratumorally with 3 weekly doses of various combinations of mAbs. Combinations of mAbs to CTLA4/PD1/CD137 (the 3 mAb combination) and to CTLA4/PD1/CD137/CD19 (the 4 mAb combination) were most efficacious to induce complete regression of both the injected tumor and an untreated tumor in the same mouse...
October 2018: Journal of Immunotherapy
Umang Swami, Yousef Zakharia, Jun Zhang
Over the past couple of years, human microbiome has received increasing attention as a regulator and predictor of response to the therapies of various diseases. It is speculated that manipulating gut microbiome can modify response to cancer immunotherapies as well. Through this review, we have critically analyzed our current understanding of gut microbiome as a modulator of immunotherapies in lung cancer, explained conflicting data, evaluated current gaps and extrapolated our present knowledge to generate directions for future investigations...
October 2018: Journal of Immunotherapy
Haneen Shalabi, Pamela L Wolters, Staci Martin, Mary Anne Toledo-Tamula, Marie Claire Roderick, Kari Struemph, Eli Kane, Bonnie Yates, Cindy Delbrook, Crystal L Mackall, Daniel W Lee, Terry J Fry, Nirali N Shah
Neurotoxicity associated with CAR-T cell therapy can be life-threatening. With rapid development of CAR-T therapies, a systematic method is needed to identify and monitor symptoms of neurotoxicity, elucidate potential etiologies, and compare toxicity across trials. This paper presents a systematic evaluation developed and used to prospectively assess neurotoxicity in our phase I anti-CD22 CAR-T-cell trial and describes the symptoms of neurotoxicity identified using this methodology. Central nervous system (CNS) studies included routine lumbar punctures performed for disease evaluation pretherapy and posttherapy and a baseline brain MRI...
September 2018: Journal of Immunotherapy
Anthony Visioni, Minhyung Kim, Chandler Wilfong, Asher Blum, Colin Powers, Daniel Fisher, Emmanuel Gabriel, Joseph Skitzki
Adoptive cell transfer therapy for cancer has existed for decades and is experiencing a resurgence in popularity that has been facilitated by improved methods of production, techniques for genetic modification, and host preconditioning. The trafficking of adoptively transferred lymphocytes and infiltration into the tumor microenvironment is sine qua non for successful tumor eradication; however, the paradox of extremely poor trafficking of lymphocytes into the tumor microenvironment raises the issue of how best to deliver these cells to optimize entry into tumor tissue...
September 2018: Journal of Immunotherapy
Emily Wynja, Benjamin Solomon, Jonathan Bleeker
Checkpoint inhibitor immunotherapy has recently been proven to be an attractive treatment option for a wide variety of malignancies. Nivolumab, an anti-programmed cell death protein-1 antibody, has been proven effective and safe in treating metastatic renal cell carcinoma (RCC) with a clear cell component. We report the case of a patient with high-grade clear cell RCC with rhabdoid features who has achieved a durable complete response with nivolumab therapy after multiple surgical interventions and progression on pazopanib...
September 2018: Journal of Immunotherapy
Varun Jain, Mahsa Mohebtash, Maria E Rodrigo, George Ruiz, Michael B Atkins, Ana Barac
The immune checkpoint inhibitors have brought about a paradigm shift in the treatment of many cancers and are being used as the first line therapy in increasing number of aggressive malignancies, including metastatic melanoma. Their adverse effects, mostly mediated by an uncontrolled overactivation of the immune system, may compromise the therapeutic benefit. Combination immune checkpoint therapies in particular, have higher therapeutic efficacy, but have also been associated with a higher incidence of severe immune-related adverse effects including autoimmune lymphocytic myocarditis...
September 2018: Journal of Immunotherapy
Cathy Yunjia Zhao, Shelley Ji Eun Hwang, Rachael Anforth, Giuliana Carlos, Shaun Chou, Matteo Carlino, Pablo Fernández-Peñas
Systemic melanoma therapies have the potential to affect basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cuSCC) development. In this study, we aim to compare the incidence of BCC and cuSCC in patients with metastatic melanoma treated with antiprogrammed cell death-1 (anti-PD1), BRAF inhibitor (BRAFi) monotherapy or dabrafenib and trametinib combination therapy (CombiDT) with a group of control patients having similar risk factors. We reviewed the records of melanoma patients on anti-PD1, BRAFi, or CombiDT, and patients from the High-Risk Melanoma Clinic, Westmead Hospital...
September 2018: Journal of Immunotherapy
Ying Ying Tang, Si Yuan Sheng, Chuan Gang Lu, Yu Qing Zhang, Jian Yong Zou, Yi Yan Lei, Yong Gu, Hai Hong
The canonical Wnt-β-catenin signaling pathway arrests the differentiation of T cells and plays an important role in phenotypic maintenance of naive T cells and stem cell-like memory T cells in human peripheral blood, but its effect on tumor-infiltrating lymphocytes (TILs) from non-small cell lung cancer is little known. In this study, we showed that glycogen synthase kinase-3β inhibitor TWS119 has different effects on CD4 and CD8 T cells in TILs. TWS119 preserved the expansion of naive T cell and CD8 stem cell-like memory T cells, and induced CD8 effector T-cell proliferation in TILs...
September 2018: Journal of Immunotherapy
Ecaterina Ileana Dumbrava, Veronica Smith, Rasha Alfattal, Adel K El-Naggar, Marta Penas-Prado, Apostolia M Tsimberidou
Immune checkpoint inhibitors such as anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), anti PD-1 (programmed cell death protein 1) and PD-L1 (programmed cell death protein-ligand 1) monoclonal antibodies are emerging as standard oncology treatments in various tumor types. The indications will expand as immunotherapies are being investigated in various tumors with promising results. Currently, there is inadequate identification of predictive biomarkers of response or toxicity. Unique response patterns include pseudoprogression and delayed response...
September 2018: Journal of Immunotherapy
Daniel V P de Almeida, Jessica R Gomes, Fabio J Haddad, Antonio C Buzaid
A 69-year-old man with metastatic lung adenocarcinoma presented with pericarditis and pericardial tamponade during nivolumab treatment, despite near-complete response on images performed during response evaluation. Further investigation found no evidence of pericardial or pleural cancer involvement, and pathologic evaluation showed immune-related adverse effect. Surgical and steroid treatments were used, with excellent results, and no disease progression on follow-up despite drug discontinuation because of toxicity...
September 2018: Journal of Immunotherapy
Cheng Zhang, Pei-Yan Kong, Shiqi Li, Ting Chen, Xun Ni, Yunyan Li, Meiling Wang, Yao Liu, Lei Gao, Li Gao, Xian-Gui Peng, Ai-Hua Sun, Ping Wang, Zhi Yang, Xi Zhang, Cheng Qian
BACKGROUND: Reduced-intensity conditioning (RIC) regimens with low tolerable toxicities have been used for allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the relapse rate by this treatment is high. Treatment of CD19 B-cell relapsed/refractory acute lymphoblastic leukemia (r/r ALL) with allogeneic chimeric antigen receptor-modified T (CAR-T) cells is safe and effective. Use of allogeneic CD19-CAR-T cells as a part of RIC regimens for treatment of r/r ALL patients with haploidentical HSCT has not been investigated yet...
July 2018: Journal of Immunotherapy
Yingshi Chen, Fei Yu, Yawen Jiang, Jingliang Chen, Kang Wu, Xinxin Chen, Yingtong Lin, Hui Zhang, Linghua Li, Yiwen Zhang
Memory stem T (TSCM) cells, a new subset of memory T cells with self-renewal and multipotent capacities, are considered as a promising candidates for adoptive cellular therapy. However, the low proportion of human TSCM cells in total CD8 T cells limits their utility. Here, we aimed to induce human CD8 TSCM cells by stimulating naive precursors with interleukin-21 (IL-21). We found that IL-21 promoted the generation of TSCM cells, described as CD45RACD45ROCD62LCCR7CD122CD95 cells, with a higher efficiency than that observed with other common γ-chain cytokines...
July 2018: Journal of Immunotherapy
Kee Siang Lim, Kosaku Mimura, Ley-Fang Kua, Kensuke Shiraishi, Koji Kono
Esophageal squamous cell carcinoma (ESCC) is an aggressive upper gastrointestinal cancer and effective treatments are limited. Previous studies reported that natural killer (NK) cells expanded by coculturing with K562-mb15-41BBL feeder cells, a genetically modified K562 leukemia cell line that expresses membrane-bound interleukin (IL)-15 and 41BBL ligand, were highly proliferative and highly cytotoxic. Here, we investigated the potential of expanded NK cells for ESCC treatment. We analyzed both genetic and surface expression levels of NKG2D ligands (NKG2DLs) in ESCC using publicly available microarray data sets and ESCC cell lines...
July 2018: Journal of Immunotherapy
Jeng-Sen Tseng, Tsung-Ying Yang, Chih-Ying Wu, Wen-Hui Ku, Kun-Chieh Chen, Kuo-Hsuan Hsu, Yen-Hsiang Huang, Kang-Yi Su, Sung-Liang Yu, Gee-Chen Chang
Immunotherapy targeting the programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway has emerged as an effective treatment for lung cancer patients. It is important to evaluate the practicality of PD-L1 testing in real-world practice. A total of 211 non-small cell lung cancer patients were enrolled to detect 5 driver mutations and PD-L1 status (22C3 and SP263 assays) and to evaluate the characteristics of PD-L1 expression and its predictive value of immunotherapy. The PD-L1 positive (≥1%) and strong positive (≥50%) rate by SP263 assay was 27...
July 2018: Journal of Immunotherapy
Christine M Parseghian, Madhavi Patnana, Priya Bhosale, Kenneth R Hess, Ya-Chen Tina Shih, Bumyang Kim, Scott Kopetz, Michael J Overman, Gauri R Varadhachary, Milind Javle, Aung Naing, Sarina Piha-Paul, David Hong, Hung Le, Vivek Subbiah, Shubham Pant
Pseudoprogression has been observed in patients with various tumor types treated with immunotherapy. However, the frequency of pseudoprogression is unknown in gastrointestinal malignancies. Metastatic colorectal cancer (mCRC) and advanced pancreatic ductal adenocarcinoma (PDAC) patients who progressed on treatment with immunotherapy beyond RECIST version 1.1 criteria were analyzed. Degree of progression, tumor markers, time to progression, overall survival, Eastern Cooperative Oncology Group Performance Status (ECOG PS), and costs were analyzed for patients treated beyond progression (TBP) and not treated beyond progression...
July 2018: Journal of Immunotherapy
Dimitrios T Trafalis, Constantinos E Alifieris, Anastasios Kalantzis, Kosmas E Verigos, Chrysovalantis Vergadis, Sébastien Sauvage
Penile squamous cell carcinoma (PeSCC) is a rare tumor and advanced PeSCC is associated with poor survival due to the aggressiveness of the disease and lack of effective systemic therapies. We describe for the first time a case with advanced chemoradiation refractory PeSCC who had documented response to active immunotherapy with the immune checkpoint inhibitor, anti-programmed death-1 monoclonal antibody Nivolumab. The patient suffered from a poor prognosis human papillomavirus-negative PeSCC, with a somatic inactivation mutation of cyclin-dependent kinase inhibitor 2A (CDKN2A) gene in tumor cells, and treatment with Nivolumab resulted in a partial response to therapy and significant tumor shrinkage...
July 2018: Journal of Immunotherapy
Florentia Dimitriou, Alexandra V Matter, Joanna Mangana, Mirjana Urosevic-Maiwald, Sara Micaletto, Ralph P Braun, Lars E French, Reinhard Dummer
Switching from immunotherapy to targeted therapy in metastasized melanoma can be complicated by a cytokine release syndrome (CRS). CRS is a serious complication, which is induced by high levels of circulating cytokines, associated with T-cell engagement and proliferation, and results in a constellation of symptoms with variable organ involvement. We report 2 patients with BRAF V600 mutant melanoma who were previously treated with anti-PD-1±anti-LAG-3 antibodies and were switched to BRAF/MEK-inhibitors because of progressive disease...
June 22, 2018: Journal of Immunotherapy
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