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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
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
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
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
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