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Journal of Immunotherapy

Vivek Verma, Waqar Haque, Taylor R Cushman, Chi Lin, Charles B Simone, Joe Y Chang, Shearwood McClelland, James W Welsh
Racial and/or socioeconomic factors affect the type of therapies delivered for non-small cell lung cancer (NSCLC). Given the rapid expansion of immunotherapy for NSCLC, it is a crucial public health priority to evaluate disparities in administration thereof. The National Cancer Database (NCDB) was queried for newly diagnosed metastatic NSCLC. Patients were dichotomized based on receipt of immunotherapy-type compounds (ICs) based on NCDB coding. Multivariable logistic regression ascertained factors associated with IC delivery...
January 8, 2019: Journal of Immunotherapy
Carlen Yuen, Pankti Reid, Zuoli Zhang, Betty Soliven, Jason J Luke, Kourosh Rezania
The augmented immune response caused by immune checkpoint inhibitors leads to the emergence of a class of side effects called immune-related adverse events (irAEs). Facial palsy (FP) is rarely reported as an irAE. In this retrospective study, we reviewed the records of 353 patients treated with immunotherapy in our center from 2015-2018. We identified 4 male patients and 1 female patient with FP. Four had metastatic melanoma and were treated with ipilimumab either as monotherapy or in combination with nivolumab or pembrolizumab...
January 4, 2019: Journal of Immunotherapy
Ruidi Teng, Jingjing Zhao, Yiding Zhao, Junshuang Gao, Haibo Li, Shixin Zhou, Yuan Wang, Qiang Sun, Zhongqing Lin, Weifeng Yang, Ming Yin, Jinhua Wen, Hongkui Deng
Adoptive transfer of T cells engineered with a chimeric antigen receptor (CAR) is deemed as the silver bullet to overcome the barriers of solid tumor treatment; however, the therapeutic application against solid tumors faces major challenges largely owing to the complex heterogeneity and immunosuppressive microenvironment of solid tumors. Preclinical development of CAR-T-cell products necessitates an appropriate animal model for the evaluation and improvement of their therapeutic capacities. Patient-derived xenograft (PDX) resembles real patients in several ways, and may serve as an attractive alternative to generate and evaluate the efficacy of CAR-T-cell products...
December 20, 2018: Journal of Immunotherapy
Bartosz Grzywacz, Laura Moench, David McKenna, Katelyn M Tessier, Veronika Bachanova, Sarah Cooley, Jeffrey S Miller, Elizabeth L Courville
Cellular immunotherapy using allogeneic natural killer (NK) cells may overcome chemotherapy-refractory acute myeloid leukemia. Our goal was to document NK cell homing/persistence in the bone marrow following adoptive immunotherapy. Our cohort included 109 patients who received NK cell therapy for refractory acute myeloid leukemia following lymphodepleting conditioning +/- denileukin diftitox, +/- low-dose total body irradiation. We evaluated the NK cell density in bone marrow core biopsies performed an average of 14 days after NK cell transfer using a CD56 immunohistochemical stain...
November 27, 2018: Journal of Immunotherapy
Hadas Weinstein-Marom, Noam Levin, Aviad Pato, Nofar Shmuel, Adi Sharabi-Nov, Tamar Peretz, Galit Eisenberg, Michal Lotem, Orit Itzhaki, Michal J Besser, Gideon Gross
Adoptive transfer of tumor-infiltrating lymphocytes (TILs) or gene-modified T cells expressing antitumor TCRs or chimeric antigen receptors often yields a high rate of clinical response in several types of cancer. New approaches for enhancing the functional properties of antitumor T cells could improve the clinical outcome of these treatments. To this end, we created 3 classes of genes, each designed to operate autonomously upon expression in T cells. We recently reported on the enhancing effects of constitutively active toll-like receptor 4 (caTLR4), membrane (mem) interleukin-2, memIL-12, and memIL-15, and self-oligomerizing, constitutively active CD40 (caCD40)...
November 27, 2018: Journal of Immunotherapy
Gennaro Riccio, Ana Rita Ricardo, Margherita Passariello, Kathy Saraiva, Valentina Rubino, Philip Cunnah, Nico Mertens, Claudia De Lorenzo
The Tyrosine Kinase Receptor ErbB2 (HER2) when overexpressed in breast cancer (BC) is associated with poor prognosis. The monoclonal antibody Trastuzumab has become a standard treatment of ErbB2+BC. The antibody treatment has limited efficacy, often meets resistance and induces cardiotoxicity. T-cell recruiting bispecific antibody derivatives (TRBA) offer a more effective alternative to standard antibody therapy. We evaluated a panel of TRBAs targeting 3 different epitopes on the ErbB2 receptor either in a bivalent targeting tribody structure or as a monovalent scFv-fusion (BiTE format) for binding, cytotoxicity on Trastuzumab-resistant cell lines, and induction of cardiotoxicity...
January 2019: Journal of Immunotherapy
Peng Song, Lei Guo, Wenbin Li, Fan Zhang, Jianming Ying, Shugeng Gao
Our study was to evaluate the concordance of programmed cell death-ligand 1 (PD-L1) expression between 22C3 and SP263 assay and explore the association of clinicopathologic features with expression of PD-L1 on both tumor cells (TC) and tumor-infiltrating immune cells (IC). We retrospectively assessed the PD-L1 expression in 305 patients with lung adenocarcinoma or adenosquamous carcinoma by 22C3 and SP263 assay. The association of PD-L1 expression by 22C3 assay with clinicopathologic features was also analyzed...
November 6, 2018: Journal of Immunotherapy
Emel Sahin, Mehmet Sahin
Regulatory T cells (Treg cells), a subgroup of CD4 lymphocytes, play a crucial role in serving as an immune suppressor and in maintaining peripheral tolerance. As the accumulation of Treg cells in the tumor microenvironment is significantly associated with a decreased survival time of patients, they are considered as an important therapeutic target in the immunotherapy of human cancers. These cells are either derived from the thymus, which are called (CD4CD25CD127) natural Treg cells (nTreg cells), or they are generated from CD4CD25 naive T cells by transforming growth factor-beta 1 and interleukin 2 (IL-2) in the periphery, which are called induced Treg cells (iTreg cells)...
November 6, 2018: Journal of Immunotherapy
Melanie A Lindenberg, Valesca P Retèl, Joost H van den Berg, Marnix H Geukes Foppen, John B Haanen, Wim H van Harten
Tumor-infiltrating lymphocytes (TIL)-therapy in advanced melanoma is an advanced therapy medicinal product (ATMP) which, despite promising results, has not been implemented widely. In a European setting, TIL-therapy has been in use since 2011 and is currently being evaluated in a randomized controlled trial. As clinical implementation of ATMPs is challenging, this study aims to evaluate early application of TIL-therapy, through the application of a constructive technology assessment (CTA). First the literature on ATMP barriers and facilitators in clinical translation was summarized...
November 2018: Journal of Immunotherapy
Christian Merz, Jaromir Sykora, Viola Marschall, David M Richards, Karl Heinonen, Mauricio Redondo Müller, Meinolf Thiemann, Tim Schnyder, Harald Fricke, Oliver Hill, Christian Gieffers
CD40 ligand (TNFSF5/CD154/CD40L), a member of the tumor necrosis factor (TNF) superfamily is a key regulator of the immune system. The cognate receptor CD40 (TNFRSF5) is expressed broadly on antigen-presenting cells and many tumor types, and has emerged as an attractive target for immunologic cancer treatment. Most of the CD40 targeting drugs in clinical development are antibodies which display some disadvantages: their activity typically depends on Fcγ receptor-mediated crosslinking, and depletion of CD40-expressing immune cells by antibody-dependent cellular cytotoxicity compromises an efficient antitumor response...
November 2018: 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...
November 2018: Journal of Immunotherapy
René J Tavera, Marie-Andrée Forget, Young Uk Kim, Donastas Sakellariou-Thompson, Caitlin A Creasy, Ankit Bhatta, Orenthial J Fulbright, Renjith Ramachandran, Shawne T Thorsen, Esteban Flores, Arely Wahl, Audrey M Gonzalez, Christopher Toth, Seth Wardell, Rahmatu Mansaray, Laszlo G Radvanyi, Dan S Gombos, Sapna P Patel, Patrick Hwu, Rodabe N Amaria, Chantale Bernatchez, Cara Haymaker
In this study, we address one of the major critiques for tumor-infiltrating lymphocyte (TIL) therapy-the time needed for proper expansion of a suitable product. We postulated that T-cell receptor activation in the first phase of expansion combined with an agonistic stimulation of CD137/4-1BB and interleukin-2 would favor preferential expansion of CD8 TIL. Indeed, this novel 3-signal approach for optimal T-cell activation resulted in faster and more consistent expansion of CD8CD3 TIL. This new method allowed for successful expansion of TIL from cutaneous and uveal melanoma tumors in 100% of the cultures in <3 weeks...
November 2018: Journal of Immunotherapy
Bradley Maller, Edwin Peguero, Tawee Tanvetyanon
INTRODUCTION: Ipilimumab and nivolumab are immune-checkpoint inhibitors commonly used for melanoma. The combination is being investigated for its efficacy against several types of cancer, including malignant pleural mesothelioma. Although immune-related adverse events have been reported in patients receiving immune-checkpoint inhibitors, opsoclonus-myoclonus-ataxia syndrome has never been previously described. CASE PRESENTATION: We describe a 74-year-old male with malignant pleural mesothelioma who presented with opsoclonus and marked truncal ataxia ∼10 weeks following immunotherapy with ipilimumab and nivolumab...
November 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
Michael S Oh, Young Kwang Chae
Immune checkpoint inhibitors have shown promising efficacy in multiple cancer types. The recent food and drug administration approval of PD-1 inhibitors for mismatch repair (MMR)-deficient tumors has extended use of these treatments to all cancer types, and programmed death ligand 1 (PD-L1) positivity in tumor tissue has also been shown to predict susceptibility to immunotherapy. Despite these advances, the response to immunotherapy in endometrial cancer remains poorly understood. Here, we describe the case of a patient with MMR-proficient, PD-L1-negative stage IV endometrial cancer who exhibited a strong clinical response to combination PD-1 and CTLA-4 inhibition...
September 21, 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
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