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immune-checkpoint blockade

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https://www.readbyqxmd.com/read/28544595/severe-cytokine-release-syndrome-in-a-patient-receiving-pd-1-directed-therapy
#1
Seth J Rotz, Daniel Leino, Sara Szabo, Jennifer L Mangino, Brian K Turpin, Joseph G Pressey
Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of cellular and bispecific T-cell engaging immunotherapy. Checkpoint blockade using anti-programmed cell death 1 (anti-PD-1) inhibitors is an approach to antitumor immune system stimulation. A 29-year-old female with alveolar soft part sarcoma developed severe CRS after treatment with anti-PD-1 therapy. CRS was characterized by high fevers, encephalopathy, hypotension, hypoxia, hepatic dysfunction, and evidence of coagulopathy, and resolved after infusion of the interleukin-6 inhibitor tocilizumab and corticosteroids...
May 24, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28543699/immune-and-molecular-correlates-in-melanoma-treated-with-immune-checkpoint-blockade
#2
REVIEW
Elizabeth H Byrne, David E Fisher
Immunotherapy for metastatic melanoma has a decades-long history, and the relatively recent use of checkpoint inhibitors has revolutionized treatment. Durable and sometimes complete remission of metastatic melanoma is now achievable in some patients who receive checkpoint-blocking therapy. However, it is unclear why some patients fare better than others. This review highlights several molecular indicators of response to checkpoint inhibition in metastatic melanoma, focusing on tumor programmed death ligand 1 expression, major histocompatibility complex class I expression, mutational load in the tumor, and T-cell infiltration into the tumor...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28539557/prospects-for-personalized-combination-immunotherapy-for-solid-tumors-based-on-adoptive-cell-therapies-and-immune-checkpoint-blockade-therapies
#3
Daiki Kato, Tomonori Yaguchi, Takashi Iwata, Kenji Morii, Takayuki Nakagawa, Ryohei Nishimura, Yutaka Kawakami
  Immune checkpoint blockade (ICB) and adoptive cell therapies (ACT) with antigen-receptor gene-engineered T cells have been shown to be successful for a limited number of patients with solid tumors. Responders to ICB therapy typically have T cell-inflamed tumors. Thus, it is important to develop strategies that convert non-T cell-inflamed tumors to T cell-inflamed tumors. Although chimeric antigen receptor transduced T (CAR-T) cell therapy targeting hematological malignancies demonstrated durable clinical responses, the success of gene-engineered T cell therapies in solid tumors is hampered by a lack of unique antigens, antigen loss in cancer cells, and the immune-suppressive tumor microenvironment (TME) of solid tumors...
2017: Nihon Rinshō Men'eki Gakkai Kaishi, Japanese Journal of Clinical Immunology
https://www.readbyqxmd.com/read/28539528/prospect-of-immunotherapy-for-glioblastoma-tumor-vaccine-immune-checkpoint-inhibitors-and-combination-therapy
#4
Eiichi Ishikawa, Tetsuya Yamamoto, Akira Matsumura
To date, clinical trials of various vaccine therapies using autologous tumor antigens or tumor-associated/specific antigen peptide with adjuvants have been performed to treat patients with high-grade gliomas (HGG). Furthermore, immune checkpoint pathway-targeted therapies including anti- programmed cell death 1 (PD-1) antibody have been remarkably effective in other neoplasms, and various clinical trials with anti-PD-1 antibody in patients with HGG have started to date. It is possible that up-regulation of immune checkpoint molecules in tumor tissues after vaccine therapy may be one of the mechanisms of vaccine failure...
May 24, 2017: Neurologia Medico-chirurgica
https://www.readbyqxmd.com/read/28537896/5t4-oncofoetal-glycoprotein-an-old-target-for-a-novel-prostate-cancer-immunotherapy
#5
Federica Cappuccini, Emily Pollock, Stephen Stribbling, Adrian V S Hill, Irina Redchenko
The tumour-associated antigen 5T4 is an attractive target for cancer immunotherapy. However to date, reported 5T4-specific cellular immune responses induced by various immunisation platforms have been largely weak or non-existent. In the present study, we have evaluated a heterologous prime boost regime based on the simian adenovirus ChAdOx1 and modified vaccinia virus Ankara (MVA) expressing 5T4 for immunogenicity and tumour protective efficacy in a mouse cancer model. Vaccination-induced immune responses were strong, durable and attributable primarily to CD8+ T cells...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28536388/capitalizing-on-cancer-specific-replication-oncolytic-viruses-as-a-versatile-platform-for-the-enhancement-of-cancer-immunotherapy-strategies
#6
REVIEW
Donald Bastin, Scott R Walsh, Meena Al Saigh, Yonghong Wan
The past decade has seen considerable excitement in the use of biological therapies in treating neoplastic disease. In particular, cancer immunotherapy and oncolytic virotherapy have emerged as two frontrunners in this regard with the first FDA approvals for agents in both categories being obtained in the last 5 years. It is becoming increasingly apparent that these two approaches are not mutually exclusive and that much of the therapeutic benefit obtained from the use of oncolytic viruses (OVs) is in fact the result of their immunotherapeutic function...
August 24, 2016: Biomedicines
https://www.readbyqxmd.com/read/28536382/fifty-years-of-clinical-application-of-newcastle-disease-virus-time-to-celebrate
#7
REVIEW
Volker Schirrmacher
This review provides an overview of 50 years of basic and clinical research on an oncolytic avian virus, Newcastle Disease Virus (NDV), which has particular anti-neoplastic and immune stimulatory properties. Of special interest is the fact that this biological agent induces immunogenic cell death and systemic anti-tumor immunity. Furthermore, localized oncolytic virotherapy with NDV was shown to overcome systemic tumor resistance to immune checkpoint blockade immunotherapy. Clinical experience attests to low side effects and a high safety profile...
July 20, 2016: Biomedicines
https://www.readbyqxmd.com/read/28536305/shaping-the-tumor-stroma-and-sparking-immune-activation-by-cd40-and-4-1bb-signaling-induced-by-an-armed-oncolytic-virus
#8
Emma Eriksson, Ioanna Milenova, Jessica Wenthe, Magnus Ståhle, Justyna Leja-Jarblad, Gustav Ullenhag, Anna Dimberg, Rafael Moreno, Ramon Alemany, Angelica Loskog
PURPOSE: Pancreatic cancer is a severe indication with short expected survival despite surgery and/or combination chemotherapeutics. Checkpoint blockade antibodies are approved for several cancer indications but pancreatic cancer has remained refractory. However, there are clinical data suggesting that stimulation of the CD40 pathway may be of interest for these patients. Oncolytic viruses armed with immunostimulatory genes represent an interesting approach. Herein we present LOAd703, a designed adenovirus armed with trimerized CD40L and 4-1BBL that activate the CD40 and 4-1BB pathways, respectively...
May 23, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28536278/immune-checkpoint-blockade-immunogenic-chemotherapy-or-ifn-%C3%AE-blockade-boost-the-local-and-abscopal-effects-of-oncolytic-virotherapy
#9
Laetitia Fend, Takahiro Yamazaki, Christelle Remy, Catherine Fahrner, Murielle Gantzer, Virginie Nourtier, Xavier Préville, Eric Quéméneur, Oliver Kepp, Julien Adam, Aurélien Marabelle, Jonathan M Pitt, Guido Kroemer, Laurence Zitvogel
Athough the clinical efficacy of oncolytic viruses has been demonstrated for local treatment, the ability to induce immune-mediated regression of distant metastases is still poorly documented. We report here that the engineered oncolytic vaccinia virus VVWR-TK(-)RR(-)-Fcu1 can induce immunogenic cell death and generate a systemic immune response. Effects on tumor growth and survival was largely driven by CD8(+) T cells, and immune cell infiltrate in the tumor could be reprogrammed towards a higher ratio of effector T cells to regulatory CD4(+) T cells...
May 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28534503/tumour-vessel-normalization-and-immune-checkpoint-blockade-a-new-synergism
#10
Ruth Ganss
No abstract text is available yet for this article.
May 23, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28534250/advancing-immunotherapy-in-metastatic-breast-cancer
#11
REVIEW
Mariam Mansour, Zhi Ling Teo, Stephen J Luen, Sherene Loi
Despite many advances in the treatment of breast cancer, the development of metastatic disease remains an incurable and frequent cause of cancer death for women worldwide. An improved understanding of the role of host immunosurveillance in modulating breast cancer disease biology, as well as impressive survival benefits seen to checkpoint blockade in other malignancies have provided great hope for an expanding role of immunotherapies in breast cancer management. While these novel therapies are currently being investigated in clinical trials, signals of efficacy, and tolerability in early phase studies suggest these will eventually make their way into standard practice algorithms...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28533272/chimeric-pd-1-28-receptor-upgrades-low-avidity-t-cells-and-restores-effector-function-of-tumor-infiltrating-lymphocytes-for-adoptive-cell-therapy
#12
Ramona Schlenker, Luis Felipe Olguín-Contreras, Matthias Leisegang, Julia Schnappinger, Anja Disovic, Svenja Rühland, Peter J Nelson, Heinrich Leonhardt, Hartmann Harz, Susanne Wilde, Dolores J Schendel, Wolfgang Uckert, Gerald Willimsky, Elfriede Noessner
Inherent intermediate-to-low affinity T cell receptors (TCR) that develop during the natural course of immune responses may not allow sufficient activation for tumor elimination, making the majority of T cells suboptimal for adoptive T cell therapy (ATT). TCR affinity enhancement has been implemented to provide stronger T cell activity but carries the risk of creating undesired cross-reactivity leading to potential serious adverse effects in clinical application. We demonstrate here that engineering of low-avidity T cells recognizing a naturally processed and presented tumor-associated antigen with a chimeric PD-1:28 receptor increases effector function to levels seen with high-avidity T cells of identical specificity...
May 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28529947/immune-checkpoint-blockade-for-hematologic-malignancies-a-review
#13
REVIEW
Matthew J Pianko, Yuzhou Liu, Srishti Bagchi, Alexander M Lesokhin
Immune checkpoint blockade has revolutionized the treatment of cancer, with impressive responses seen in a broad variety of tumor types. Blockade of immune checkpoints and immune signaling antibodies has shown promise in multiple types of hematologic malignancies (HMs), with dramatic single agent responses for pembrolizumab and nivolumab in Hodgkin lymphoma (HL). In this review, we outline the current state of immune checkpoint blockade drug development in HMs, and discuss mechanisms of activity and resistance, and highlight potential targets in the immune tumor microenvironment (TME)...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28529899/clinical-experiences-of-combining-immunotherapy-and-radiation-therapy-in-non-small-cell-lung-cancer-lessons-from-melanoma
#14
REVIEW
Anusha Kalbasi, Ramesh Rengan
Radiation therapy (RT) is an essential component of local control for non-small cell lung cancer (NSCLC), but distant failures dictate the poor prognosis of this disease. Until recently, the possibility of using RT as an immunoadjuvant to stimulate a systemic anti-tumor immune response was not a realistic clinical opportunity. The emergence of immune checkpoint blockade as an effective immunotherapy for NSCLC has opened the door for combinatorial approaches involving RT. In melanoma, the body of preclinical evidence combining radiation and immunotherapy buoyed clinical efforts, from which promising results have begun to emerge...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28529897/uncovering-the-immune-tumor-microenvironment-in-non-small-cell-lung-cancer-to-understand-response-rates-to-checkpoint-blockade-and-radiation
#15
REVIEW
Jonathan E Schoenhals, Steven N Seyedin, Clark Anderson, Eric D Brooks, Yun R Li, Ahmed I Younes, Sharareh Niknam, Ailin Li, Hampartsoum B Barsoumian, Maria Angelica Cortez, James W Welsh
The study of immunology has led to breakthroughs in treating non-small cell lung cancer (NSCLC). The recent approval of an anti-PD1 checkpoint drug for NSCLC has generated much interest in novel combination therapies that might provide further benefit for patients. However, a better understanding of which combinations may (or may not) work in NSCLC requires understanding the lung immune microenvironment under homeostatic conditions and the changes in that microenvironment in the setting of cancer progression and with radiotherapy...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28528510/immunogenomics-using-genomics-to-personalize-cancer-immunotherapy
#16
Rance C Siniard, Shuko Harada
While the use of genomic data has the potential to revolutionize patient care, there is still much work to be done with regard to the transformation of host-tumor interactions into favorable clinical outcomes for our patients. High-throughput technologies, such as next-generation sequencing (NGS), have rapidly advanced our understanding of oncology, and we are learning that most tumors do not simply possess consistently mutated genes that are responsible for tumorigenesis, facilitating the need for personalized cancer therapy...
May 20, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28527652/uveitis-induced-by-programmed-cell-death-protein-1-inhibitor-therapy-with-nivolumab-in-metastatic-melanoma-patient
#17
Hiroaki Kanno, Kyoko Ishida, Wataru Yamada, Takashi Nishida, Nobumichi Takahashi, Kiyofumi Mochizuki, Yuki Mizuno, Kanako Matsuyama, Tomoko Takahashi, Mariko Seishima
Nivolumab, a new immune checkpoint inhibitor, binds to programmed cell death-protein 1 receptors on T cell, blockades binding of its ligands, and augments the immunologic reaction against tumor cells. Augmented immune response, however, may lead to immune-related adverse events. Herein we describe a rare case of bilateral anterior uveitis induced by nivolumab treatment for metastatic melanoma. A 54-year-old woman presented with mild conjunctival redness and blurred vision two months after initiating nivolumab treatment...
May 17, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28525897/a-cellular-platform-for-the-evaluation-of-immune-checkpoint-molecules
#18
Sabrina Jutz, Annika Hennig, Wolfgang Paster, Ömer Asrak, Dejana Dijanovic, Florian Kellner, Winfried F Pickl, Johannes B Huppa, Judith Leitner, Peter Steinberger
Blockade of the T cell coinhibitory molecules CTLA-4 and PD-1 has clinical utility to strengthen T cell responses. In addition to these immune checkpoints an ever-growing number of molecules has been implicated in generating coinhibitory signals in T cells. However, investigating coinhibitory molecules in primary human cells is complicated by the restricted expression and promiscuity of both coinhibitory receptors and their ligands. Here we have evaluated the potential of fluorescence-based transcriptional reporters based on the human Jurkat T cell line in conjunction with engineered T cell stimulator cell lines for investigating coinhibitory pathways...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524159/hallmarks-of-response-to-immune-checkpoint-blockade
#19
Alexandria P Cogdill, Miles C Andrews, Jennifer A Wargo
Unprecedented advances have been made in the treatment of cancer through the use of immune checkpoint blockade, with approval of several checkpoint blockade regimens spanning multiple cancer types. However, responses to this form of therapy are not universal, and insights are clearly needed to identify optimal biomarkers of response and to combat mechanisms of therapeutic resistance. A working knowledge of the hallmarks of cancer yields insight into responses to immune checkpoint blockade, although the focus of this is rather tumour-centric and additional factors are pertinent, including host immunity and environmental influences...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28522460/soluble-pd-l1-as-a-biomarker-in-malignant-melanoma-and-checkpoint-blockade
#20
Jun Zhou, Kathleen M Mahoney, Anita Giobbie-Hurder, Fengmin Zhao, Sandra Lee, Xiaoyun Liao, Scott Rodig, Jingjing Li, Xinqi Wu, Lisa H Butterfield, Matthias Piesche, Michael P Manos, Lauren M Eastman, Glenn Dranoff, Gordon J Freeman, F Stephen Hodi
Blockade of the pathway including Programmed death-ligand 1 (PD-L1) and its receptor Programmed cell death protein 1 (PD-1) has produced clinical benefits in patients with a variety of cancers.  Elevated levels of soluble PD-L1 (sPD-L1) have been associated with worse prognosis in renal cell carcinoma and multiple myeloma.  However, the regulatory roles and function of sPD-L1 particularly in connection with immune checkpoint blockade treatment are not fully understood.  We identified four splice variants of PD-L1 in melanoma cells, and all of them are secreted...
May 18, 2017: Cancer Immunology Research
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