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https://www.readbyqxmd.com/read/28803721/conditioning-neoadjuvant-therapies-for-improved-immunotherapy-of-cancer
#1
REVIEW
Zachary Benson, Saeed H Manjili, Mehran Habibi, Georgi Guruli, Amir A Toor, Kyle K Payne, Masoud H Manjili
Recent advances in the treatment of melanoma and non-small cell lung cancer (NSCLC) by combining conventional therapies with anti-PD1/PD-L1 immunotherapies, have renewed interests in immunotherapy of cancer. The emerging concept of conventional cancer therapies combined with immunotherapy differs from the classical concept in that it is not simply taking advantage of their additive anti-tumor effects, but it is to use certain therapeutic regimens to condition the tumor microenvironment for optimal response to immunotherapy...
August 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28776778/eruptive-keratoacanthomas-arising-in-the-setting-of-lichenoid-toxicity-after-pd1-inhibition-with-nivolumab
#2
Stephanie I Feldstein, Forum Patel, Larissa Larsen, Edward Kim, Samuel Hwang, Maxwell A Fung
We were fascinated to read the observations of Bandino et al. who described two patients who developed keratoacanthomas and squamous cell carcinoma in association with bullous pemphigoid-like lesions after treatment with PD-1 inhibitors, nivolumab or pembrolizumab, in a recent issue of the Journal. Herein we report two patients with no prior history of skin cancer who developed eruptive keratoacanthomas in the setting of lichenoid skin toxicity after starting nivolumab. This article is protected by copyright...
August 3, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28739716/clinical-significance-of-pd1-and-pdl1-in-human-breast-cancer
#3
Michal Uhercik, Andrew J Sanders, Sioned Owen, Eleri L Davies, Anup K Sharma, Wen G Jiang, Kefah Mokbel
BACKGROUND/AIM: Programmed death 1 (PD1) and its ligand programmed death ligand 1 (PDL1) form a pathway which when activated is thought to result in suppression of antitumor adaptive responses, influencing antitumor immunity. With potential targeted therapies emerging against PDL1, we investigated the clinical significance of mRNA expression levels of PD1 and PDL1 in our breast cancer cohort to explore its association with disease progression and prognosis. Previous studies evaluating the expression of PD1 and PDL1 (mRNA or protein) and its association with prognosis in breast cancer showed both positive and negative correlations and hence remain controversial...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28735186/development-of-a-robust-reporter-gene-assay-to-measure-the-bioactivity-of-anti-pd-1-anti-pd-l1-therapeutic-antibodies
#4
Lan Wang, Chuanfei Yu, Yalan Yang, Kai Gao, Junzhi Wang
Being regarded as the 'cancer panacea', the anti-PD-1/anti-PD-L1 monoclonal antibodies (mAbs) have become the R&D focus of biopharmaceutical industries. Several marketed such mAbs have been proved particularly effective in treating various cancers. However, the cell-based bioassay to measure the biological activities of the anti-PD-1/anti-PD-L1 mAbs as the lot release or stability test has been a great challenge to quality control laboratories due to the immunomodulating nature of the mAbs. Here, we describe the development and validation of a reporter gene assay consisting of two-cell systems to measure the bioactivity of the anti-PD-1/anti-PD-L1 mAbs...
May 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28733529/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#5
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28714780/atezolizumab-for-the-treatment-of-non-small-cell-lung-cancer
#6
Fernando C Santini, Charles M Rudin
The immune system can restrain or promote cancer development and growth. Antibodies targeting immune checkpoints have revolutionized cancer treatment. Among the best responses have been in non-small cell lung cancer (NSCLC) which is largely caused by chronic exposure to carcinogens; associated with high neoantigen creation and sensitization to immune recognition. Atezolizumab was the first approved antibody that targets the PD-1 ligand (PD-L1). Areas covered: This drug profile article covers the basics of the cancer-immunity cycle and reviews some aspects of innate and adaptive immunology...
July 27, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28708863/negative-modulation-of-suppressive-hiv-specific-regulatory-t-cells-by-il-2-adjuvanted-therapeutic-vaccine
#7
Vedran Brezar, Lylia Hani, Mathieu Surenaud, Audrey Hubert, Christine Lacabaratz, Jean-Daniel Lelièvre, Yves Levy, Nabila Seddiki
The potential benefit in using IL-2 in immunotherapy for cancer and autoimmunity has been linked to the modulation of immune responses, which partly relies on a direct effect on Tregs populations. Here, we revisited the role of IL-2 in HIV infection and investigated whether its use as an adjuvant with therapeutic vaccination, impacts on HIV-specific responses. Antiretroviral therapy treated-patients were randomized to receive 4 boosts of vaccination (ALVACHIV/Lipo-6T, weeks 0/4/8/12) followed by 3 cycles of IL-2 (weeks 16/24/32) before treatment interruption (TI) at week40...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28707167/supportive-care-for-patients-undergoing-immunotherapy
#8
Bernardo Leon Rapoport, Ronwyn van Eeden, Vincent Sibaud, Joel B Epstein, Jean Klastersky, Matti Aapro, Devan Moodley
Immune checkpoint inhibitors, a new class of cancer therapeutic agents, play an important role in the management of melanoma, NSCLC, and other malignancies. A workshop organized by three MASCC Study Groups: Oral Care, Skin Toxicities, and Neutropenia, Infection, and Myelosuppression during the MASCC Annual Meeting held in Adelaide, Australia on 23-25 June, 2016 focused on the new class of anti-cancer therapeutic agents. Topics in the workshop included the mechanism of action and clinical uses of immune anti-CTL4 and anti-PD1 antibodies, checkpoint inhibitor toxicities, including skin adverse events, gastrointestinal toxicities, oral complications, pulmonary toxicities, and endocrinological and immune-related infections...
July 13, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28700789/hair-repigmentation-during-immunotherapy-treatment-with-an-anti-programmed-cell-death-1-and-anti-programmed-cell-death-ligand-1-agent-for-lung-cancer
#9
Noelia Rivera, Aram Boada, M Isabel Bielsa, M Teresa Fernández-Figueras, Enric Carcereny, M Teresa Moran, Carlos Ferrándiz
Importance: New targeted therapies for cancer have been released in recent years, opening new horizons in the treatment of patients with cancer. However, their related adverse events (AE) are not fully characterized. Hair repigmentation (HR) is a nondescribed effect secondary to anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1 ) therapy for treatment of lung cancer (LC), in opposition to the vitiligo reactions that develop during melanoma treatment...
July 12, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28684311/hippo-effector-yap-directly-regulates-the-expression-of-pd-l1-transcripts-in-egfr-tki-resistant-lung-adenocarcinoma
#10
Byung Soo Lee, Dong Il Park, Da Hye Lee, Jeong Eun Lee, Min-Kyung Yeo, Yeon Hee Park, Dae Sik Lim, Wonyoung Choi, Da Hye Lee, Geon Yoo, Han-Byul Kim, Dahyun Kang, Jae Young Moon, Sung Soo Jung, Ju Ock Kim, Sang Yeon Cho, Hee Sun Park, Chaeuk Chung
Developments of EGFR-TKI and immunotherapy targeting the PD1/PD-L1 pathway are considered most important medical breakthroughs in lung cancer treatment. Nowadays, 3rd generation EGFR TKI is widely used for T790M positive 1st and 2nd EGFR-TKI resistant lung cancer patients. Immunotherapy is powerful option for lung cancer patients without drug targets and chemotherapy resistant patients. It also has changed the concept of conventional anti-cancer therapy in the point of regulating tumor microenvironment. There are many studies linking these two important pathways...
July 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28684274/construction-of-high-level-prokaryotic-expression-and-purification-system-of-pd-l1-extracellular-domain-by-using-escherichia-coli-host-cell-machinery
#11
Muhammad Kalim, Jie Chen, Shenghao Wang, Caiyao Lin, Saif Ullah, Keying Liang, Qian Ding, Shuqing Chen, Jinbiao Zhan
Programmed cell death 1 ligand 1 (PD-L1) is a trans-membrane protein highly expressed on the membrane of cancer cell, which binds inhibitory receptor of PD-1 on the T cells and attenuates anti-tumor immune response.The strategy of blocking PD1 and PD-L1 interaction has been widely used for anti-cancer drug development. The DNA encoding extracellular domain of PD-L1 was cloned and expressed with the pET30(+) and Escherichia coli BL21(DE3) system. Cloning of PD-L1 extracellular domain was confirmed by PCR and enzymatic digestion...
July 3, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28680755/bispecific-antibody-does-not-induce-t-cell-death-mediated-by-chimeric-antigen-receptor-against-disialoganglioside-gd2
#12
Sayed Shahabuddin Hoseini, Konstantin Dobrenkov, Dmitry Pankov, Xiaoliang L Xu, Nai-Kong V Cheung
Chimeric antigen receptors (CAR) and bispecific antibodies (BsAb) are two powerful immunotherapy approaches for retargeting lymphocytes toward cancer cells. Despite their success in lymphoblastic leukemia, solid tumors have been more recalcitrant. Identifying therapeutic barriers facing CAR-modified (CART) or BsAb-redirected T (BsAb-T) cells should facilitate their clinical translation to solid tumors. Novel lentiviral vectors containing low-affinity or high-affinity 4-1BB second-generation anti-GD2 (disialoganglioside) CARs were built to achieve efficient T cell transduction...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28671973/pd-l1-expression-in-pleomorphic-spindle-cell-and-giant-cell-carcinoma-of-the-lung-is-related-to-ttf-1-p40-expression-and-might-indicate-a-worse-prognosis
#13
Violaine Yvorel, Arnaud Patoir, François Casteillo, Claire Tissot, Pierre Fournel, Marie-Laure Stachowicz, Georgia Karpathiou, Olivier Tiffet, Michel Péoc'h, Fabien Forest
Lung sarcomatoid carcinoma of the lung is a rare tumor with a poor prognosis. More than 90% of them are pleomorphic, spindle cell and giant cell carcinoma (PSCGCC). This rare subtype of lung cancer is thought to be more resistant to chemotherapy, and a small subset of them seems to exhibit targetable mutations. Immunotherapy against PD1/PDL-1 is a new emerging treatment, and might be of interest in PSGSCC because they frequently express PD-L1. The aim of our work is to evaluate PD1 and PDL-1 expression in a surgical series of lung PSCGCC and their relationship with morphological and immunohistochemical parameters and prognosis...
2017: PloS One
https://www.readbyqxmd.com/read/28671728/clonality-analysis-of-synchronous-gastroesophageal-junction-carcinoma-and-distal-gastric-cancer-by-whole-exome-sequencing
#14
Xiaofang Xing, Shuqin Jia, Jianmin Wu, Qin Feng, Bin Dong, Bo Li, Yongning Jia, Fei Shan, Ying'ai Li, Yan Zhang, Ying Hu, Xiaodong Wang, Xiangtao Liu, Shiwei Yu, Lianhai Zhang, Zhaode Bu, Aiwen Wu, Ziyu Li, Jiafu Ji
Gastroesophageal junction (GEJ) carcinoma and distal gastric cancer (GC) have distinct epidemiology and clinical features and their relationship is uncertain. Synchronous multiple gastric cancers located mostly at proximal and distal sites provide rare specimens for investigating the comprehensive genomic relationships among these cancers in the context of identical genetic circumstances. Formalin-fixed, paraffin-embedded (FFPE) samples from 12 patients with synchronous GEJ carcinoma and distal GC were collected in this study...
July 3, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28670716/adoptive-transfer-of-murine-t-cells-expressing-a-chimeric-pd1-dap10-receptor-as-an-immunotherapy-for-lymphoma
#15
Adam Lynch, William Hawk, Emily Nylen, Sean Ober, Pierre Autin, Amorette Barber
Adoptive transfer of T cells is a promising cancer therapy and expression of chimeric antigen receptors can enhance tumour recognition and T-cell effector functions. The programmed death protein 1 (PD1) receptor is a prospective target for a chimeric antigen receptor because PD1 ligands are expressed on many cancer types, including lymphoma. Therefore, we developed a murine chimeric PD1 receptor (chPD1) consisting of the PD1 extracellular domain fused to the cytoplasmic domain of CD3ζ. Additionally, chimeric antigen receptor therapies use various co-stimulatory domains to enhance efficacy...
July 3, 2017: Immunology
https://www.readbyqxmd.com/read/28662677/a-phase-i-ii-trial-of-fixed-dose-stereotactic-body-radiotherapy-with-sequential-or-concurrent-pembrolizumab-in-metastatic-urothelial-carcinoma-evaluation-of-safety-and-clinical-and-immunologic-response
#16
Nora Sundahl, Katrien De Wolf, Sylvie Rottey, Karel Decaestecker, Daan De Maeseneer, Annabel Meireson, Els Goetghebeur, Valérie Fonteyne, Sofie Verbeke, Pieter De Visschere, Dries Reynders, Mireille Van Gele, Lieve Brochez, Piet Ost
BACKGROUND: Current first-line standard of therapy for metastatic urothelial carcinoma is platinum-based combination chemotherapy. Pembrolizumab in phase III has demonstrated a promising overall response rate of 21.1% in patients with progression or recurrence after platinum-based chemotherapy. Preclinical and clinical evidence suggests that radiotherapy has a systemic anti-cancer immune effect and can increase the level of PD-L1 and tumor infiltrating lymphocytes in the tumor microenvironment...
June 29, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28661584/clinical-and-palliative-care-outcomes-for-patients-of-poor-performance-status-treated-with-antiprogrammed-death-1-monoclonal-antibodies-for-advanced-melanoma
#17
Annie Wong, Molly Williams, Donna Milne, Kortnye Morris, Peter Lau, Odette Spruyt, Sonia Fullerton, Grant McArthur
BACKGROUND: Antiprogrammed death-1 antibodies (anti-PD1) have response rates of 40% in metastatic melanoma. Patients with poor performance status (PS) were excluded from clinical trials, yet use of anti-PD1 is widespread in clinical practice. Literature regarding clinical and palliative care outcomes in patients with poor PS treated with anti-PD1 is lacking. METHODS: Retrospective review of outcomes for all patients with advanced melanoma treated with anti-PD1 between 2012 and June 2015 at Peter MacCallum Cancer Centre, a tertiary specialist cancer center in Australia...
June 29, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28653522/-immunotherapy-and-non-small-cell-lung-cancer-a-r-evolution
#18
T Berghmans, A P Meert
Immunotherapy renews in non-small cell lung cancer. Antibodies directed against PD1 and PD-L1, blocking the relationship between the cancer cells and the immune system, allowed in randomised trials to significantly improve cancer control with an interesting survival impact of treated patients. However, it remains to determine the most benefiting populations from this expensive and potentially toxic therapy.
2017: Revue Médicale de Bruxelles
https://www.readbyqxmd.com/read/28646041/concurrent-ox40-and-cd30-ligand-blockade-abrogates-the-cd4-driven-autoimmunity-associated-with-ctla4-and-pd1-blockade-while-preserving-excellent-anti-cd8-tumor-immunity
#19
Maher G Nawaf, Maria H Ulvmar, David R Withers, Fiona M McConnell, Fabrina M Gaspal, Gwilym J Webb, Nick D Jones, Hideo Yagita, James P Allison, Peter J L Lane
Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects...
August 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28636292/-head-and-neck-cancer-promising-results-of-immunotherapy
#20
Aurélie Sivade, Djamila Bensaid, Yan Monnier, Keyvan Shabafrouz, Hanan Bouchaab, Valérie Cristina
Immunotherapy, especially checkpoint inhibitors such as anti-PD1 and anti-PDL1 antibodies, has changed the standard of care and the prognosis of melanoma, but also more recently of lung cancer, renal cancer and Hodgkin lymphoma. Results of preliminary studies in head and neck squamous cell carcinoma (HNSCC) as well as in less frequent tumors of the region, such as nasopharyngeal carcinoma and high grade salivary gland carcinoma, are also promising. Indeed, in a recent phase 3 study, the PD1 inhibitor nivolumab has recently demonstrated a significant improvement in overall survival for platin-resistant recurrent and/or metastatic HNSCC...
May 17, 2017: Revue Médicale Suisse
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