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T cell cancer therapy

David J Sher, Abiy Agiro, Siting Zhou, Andrew T Day, Andrea DeVries
Importance: Definitive radiotherapy (RT) and primary surgery (PS) are considered to be equally viable local therapy modalities for oropharyngeal squamous cell carcinoma (OPSCC). The comparative effectiveness of these therapies is often debated, and treatment decisions are based on a paucity of comparative data. Objective: To examine the differences in overall survival and key toxic effects in patients with OPSCC treated with RT and PS. Design, Setting, and Participants: This retrospective cohort analysis used the HealthCore Integrated Research Database to identify 884 patients diagnosed with OPSCC from January 1, 2007, to December 31, 2014...
September 20, 2018: JAMA Otolaryngology—Head & Neck Surgery
Charu Aggarwal, Jeffrey C Thompson, Taylor A Black, Sharyn I Katz, Ryan Fan, Stephanie S Yee, Austin L Chien, Tracey L Evans, Joshua M Bauml, Evan W Alley, Christine A Ciunci, Abigail T Berman, Roger B Cohen, David B Lieberman, Krishna S Majmundar, Samantha L Savitch, Jennifer J D Morrissette, Wei-Ting Hwang, Kojo S J Elenitoba-Johnson, Corey J Langer, Erica L Carpenter
Importance: The clinical implications of adding plasma-based circulating tumor DNA next-generation sequencing (NGS) to tissue NGS for targetable mutation detection in non-small cell lung cancer (NSCLC) have not been formally assessed. Objective: To determine whether plasma NGS testing was associated with improved mutation detection and enhanced delivery of personalized therapy in a real-world clinical setting. Design, Setting, and Participants: This prospective cohort study enrolled 323 patients with metastatic NSCLC who had plasma testing ordered as part of routine clinical management...
October 11, 2018: JAMA Oncology
Austin Lunney, Allan Haynes, Pranav Sharma
PURPOSE: Non - muscle - invasive bladder cancer (NMIBC) can recur despite transurethral resection (TURBT) and adjuvant intravesical therapy. Tobacco products excreted in the urine are hypothesized to cause tumor - promoting effects on urothelial cells through direct contact. We determined if moderate or severe lower urinary tract symptoms (LUTS) (defined as International Prostate Symptom Score [IPSS] ≥ 8) was associated with increased tumor recurrence. MATERIALS AND METHODS: We retrospectively identified 70 consecutive men initially diagnosed with NMIBC at our institution from 2010 - 2016...
September 20, 2018: International Braz J Urol: Official Journal of the Brazilian Society of Urology
Si Lin Koo, Who Whong Wang, Han Chong Toh
In recent years, the impressive number of cancer immunotherapy drugs approved has been unprecedented-building on over a century of understanding on how the immune system combats cancer, and how cancer evades it. Leading the charge are the immune checkpoint inhibitor monoclonal antibodies, and adoptive cell therapy with chimeric- antigen-receptor (CAR)-T cell therapy. These breakthrough therapies have led to improved survival in patients with many advanced cancers. Some of the clinical outcomes have been striking, and may even be potentially curative in some terminal cancer patients...
September 2018: Annals of the Academy of Medicine, Singapore
Heide Schatten
Despite significant progress in early detection and improved treatment modalities prostate cancer remains the second leading cause of cancer death in American men which results in about 30,000 deaths per year in the USA. An aggressive phenotype leading to 2.58% risk of dying from prostate cancer still exists and immunotherapy has offered new possibilities to treat metastatic prostate cancer that cannot be treated by other modalities. Cancer immunotherapy is a rapidly growing field of research aimed at identifying biomarkers in immunodiagnosis and to develop new therapies by enabling the immune system to detect and destroy cancer cells...
2018: Advances in Experimental Medicine and Biology
Samantha T Tucci, Jai W Seo, Hamilton Kakwere, Azadeh Kheirolomoom, Elizabeth S Ingham, Lisa M Mahakian, Sarah Tam, Spencer Tumbale, Mo Baikoghli, R Holland Cheng, Katherine W Ferrara
Squalenoylation of gemcitabine, a front-line therapy for pancreatic cancer, allows for improved cellular-level and system-wide drug delivery. The established methods to conjugate squalene to gemcitabine and to form nanoparticles (NPs) with the squalenoylated gemcitabine (SqGem) conjugate are cumbersome, time-consuming and can be difficult to reliably replicate. Further, the creation of multi-functional SqGem-based NP theranostics would facilitate characterization of in vivo pharmacokinetics and efficacy. Methods : Squalenoylation conjugation chemistry was enhanced to improve reliability and scalability using tert-butyldimethylsilyl (TBDMS) protecting groups...
2018: Nanotheranostics
Lindsey Hathaway, Jeremy Michael Sen, Michael Keng
Relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) is associated with a poor prognosis in both children and adults. Traditionally, there were limited options for salvage therapy, which consisted mostly of conventional chemotherapy. However, in the past 5 years, novel agents have changed our treatment strategies in this population. Blinatumomab, a bispecific CD19 directed CD3 T-cell engager, has shown to be effective in both minimal residual disease and R/R B-cell ALL. In R/R B-cell ALL, blinatumomab was associated with an improved median overall survival of 7...
2018: Patient related Outcome Measures
Rutika Mehta, Anand Shah, Khaldoun Almhanna
Gastric and esopahgeal cancers account for the six most common causes of cancer death worldwide. Locally advanced resectable cancers have a 5-year life expectancy of 30%. Despite use of chemotherapy, median overall survival for stage IV cancer rarely exceeds 1 year. A subset of gastric cancers such as microsatellite-instable tumor and Epstein-Barr virus-positive tumors have a rich immune infiltrate that makes them more responsive to immune-directed therapies. Tumors can evade T-cell-mediated "immune surveillance" by activating the programmed cell death receptor 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway...
2018: OncoTargets and Therapy
Rafael Moreno, Carlos Alberto Fajardo, Marti Farrera-Sal, Ana Judith Perisé-Barrios, Álvaro Morales-Molina, Ahmed Abdullah Al-Zaher, Javier Garcia-Castro, Ramon Alemany
Several studies have evaluated the efficacy of using human oncolytic adenovirus-loaded mesenchymal stem cells for cancer treatment. For example, we have described the antitumor efficacy of CELYVIR, autologous bone marrow mesenchymal stem cells infected with the oncolytic adenovirus ICOVIR-5, for treatment of neuroblastoma patients. Results from this clinical trial point out the role of the immune system in the clinical outcome. In this context, a better understanding of the immunophenotypic changes of human mesenchymal stem cells upon adenoviral infection and how these changes affect human autologous or allogeneic peripheral blood mononuclear cells (PBMCs) could guide strategies to improve the antitumor efficacy of infected Mesenchymal Stem Cells (MSCs)...
October 15, 2018: Molecular Cancer Therapeutics
Shuang G Zhao, Jonathan Lehrer, S Laura Chang, Rajdeep Das, Nicholas Erho, Yang Liu, Martin Sjöström, Robert B Den, Stephen J Freedland, Eric A Klein, R Jeffrey Karnes, Edward M Schaeffer, Melody Xu, Corey Speers, Paul L Nguyen, Ashley E Ross, June M Chan, Matthew R Cooperberg, Peter R Carroll, Elai Davicioni, Lawrence Fong, Daniel E Spratt, Felix Y Feng
Background: Immunotherapy has been less successful in treating prostate cancer than other solid tumors. We sought to better understand the immune landscape in prostate cancer and identify immune-related biomarkers and potential therapeutic targets. Methods: We analyzed gene expression data from 7826 prospectively collected prostatectomy samples (2013-2016), and 1567 retrospective samples with long-term clinical outcomes, for a total of 9393 samples, all profiled on the same commercial clinical platform in a CLIA-certified lab...
October 13, 2018: Journal of the National Cancer Institute
Daniel M Altmann
The field of cancer immunology stepped into the limelight this year when James P. Allison and Tasuku Honjo received the Nobel Prize in Physiology or Medicine for their discovery of cancer therapy by inhibition of negative immune regulation. Among many exciting advances contributing to the coming of age of tumour immunology as a viable clinical specialty has been the ability to progress from the initial elucidation of tumour antigens, such as the melanoma antigen, MAGE-1, to high-throughput sequencing facilitating identification of T cell epitopes from diverse tumour neoantigens...
November 2018: Immunology
Suneel D Kamath, Priya U Kumthekar
While the CNS has long been viewed as an immune-privileged environment, a paradigm shift in neuro-immunology has elevated the role of systemic immunotherapy for the treatment of metastatic disease. Increasing knowledge regarding the presence of a CNS lymphatic system and the physical and biochemical alteration of the blood brain barrier (BBB) by the tumor microenvironment suggests immune cell trafficking in and out of the CNS is possible. Emerging clinical data suggest immune checkpoint inhibitors (ICIs) can stimulate T cells peripherally to in turn have anti-tumor effects in the CNS...
2018: Frontiers in Oncology
Federica Costa, Rituparna Das, Jithendra Kini Bailur, Kavita Dhodapkar, Madhav V Dhodapkar
Despite major improvements in the treatment landscape, most multiple myeloma (MM) patients eventually succumb to the underlying malignancy. Immunotherapy represents an attractive strategy to achieve durable remissions due to its specificity and capacity for long term memory. Activation of immune cells is controlled by a balance of agonistic and inhibitory signals via surface and intracellular receptors. Blockade of such inhibitory immune receptors (termed as "immune checkpoints") including PD-1/PD-L1 has led to impressive tumor regressions in several cancers...
2018: Frontiers in Immunology
Enrique Corapi, Gustavo Carrizo, Daniel Compagno, Diego Laderach
The identification of effective new therapies for prostate cancer (PCa) requires a better understanding of the multiple molecular interactions between tumor cells and their associated microenvironment. In this context, galectin-1 (Gal-1) is a key molecule in the determination of the prostatic carcinoma microenviroment; therefore, it is essential to understand all the molecular processes in which this protein is involved. Most of the previous studies found in the literature have focused on the microenvironment remodeling properties of tumor-secreted Gal-1, through its interactions with the glyco-receptors at the cell membrane and the extracellular matrix...
2018: Frontiers in Immunology
Frank J Ward, Lekh N Dahal, Rasha Abu-Eid
Head and neck cancers (HNC) represent a heterogeneous cluster of aggressive malignancies that account for 3% of all cancer cases in the UK. HNC is increasing in frequency particularly in the developing world, which is related to changes in risk factors. Unfortunately, the mortality rate is high, which is chiefly attributed to late diagnosis at stages where traditional treatments fail. Cancer immunotherapy has achieved great successes in anti-tumor therapy. Checkpoint inhibitor (CI) antibodies enhance anti-tumor activity by blocking inhibitory receptors to drive tumor-specific T and NK cell effector responses...
2018: Frontiers in Immunology
Mehmet Akce, Mohammad Y Zaidi, Edmund K Waller, Bassel F El-Rayes, Gregory B Lesinski
Pancreatic cancer has a dismal prognosis and effective treatment options are limited. It is projected to be the second most common cause of cancer related mortality in the United States by 2030 and there is urgent unmet need for novel systemic treatment options. Immunotherapy with antibodies targeting PD-1, PD-L1, CTLA-4 has not shown clinical activity in unselected pancreatic cancer, emphasizing the need for combination immunotherapy approaches or other therapeutic strategies. As such, chimeric antigen receptor (CAR) T cell therapy represents an emerging therapeutic option for pancreatic cancer...
2018: Frontiers in Immunology
Dongmei Wang, Rui Shi, Qinglong Wang, Jianqiang Li
Philadelphia chromosome-positive (Ph-positive) acute leukemia (ALL) accounts for around one quarter of adult cases of ALL and is usually associated with poor prognosis. The patients still encounter a high rate of relapse even after they receive hematopoietic stem cell transplantation (HSCT). HSCT is considered the established therapy and best option for many malignant ALL cases, however, disease relapse remains the main reason of failure. In recent years, chimeric antigen receptor (CAR) T-cell therapy has become a promising treatment for patients with advanced blood cancers...
2018: OncoTargets and Therapy
Ana Victoria Ojeda, María José Ledo, José Luís Alvarez-Ossorio
Prostate Cancer is the second most frequent malignant neoplasm in males in the world. At the end of the disease, when the tumor becomes resistant to castration, we have a wide range of treatment possibilities aimed at the Androgenic Receptor, androgens synthesis, the skeleton, chemotherapy, and even new molecular targets that are still under investigation. Today, the best sequence of treatment for each patient has not been established yet. OBJECTIVE: The objective of this work is to review the current scene of treatment in castrate resistant prostate cancer, as well as the latest developments and strategies to choose the best sequence in each patient...
September 2018: Archivos Españoles de Urología
Bernardino Miñana López, Felipe Villacampa Aubá, Fernando Ramón de Fata Chillón, Francisco Javier Ancizu Markert, Angel García Cortés, Pablo Doménech López, Santiago Chiva San Román, José María Velis Campillo, Fernando Díez-Caballero Alonso, José Enrique Robles García, David Rosell Costa, Juan Ignacio Pascual Piédrola
We review the role of immunotherapy in castration resistant prostate cancer. Two immunotherapeutic strategies have been applied, isolated or in combination, either with each other or with other agents with demonstrated efficacy in this scenario that would play a role as immunomodulators: vaccines or monoclonal antibodies aimed to block immune response checkpoint inhibitors. Although CRPC presents, a priori, characteristics suggesting that immunotherapy may play a relevant role as a therapeutic strategy, its clinical application has demonstrated a limited and heterogeneous activity, in terms of proportion of responders and response intensity...
September 2018: Archivos Españoles de Urología
Amit Maity, Rosemarie Mick, Alexander C Huang, Sangeeth M George, Michael D Farwell, John N Lukens, Abigail T Berman, Tara C Mitchell, Josh Bauml, Lynn M Schuchter, Mark O'Hara, Lilie L Lin, Angela Demichele, John P Christodouleas, Naomi B Haas, Dana M Patsch, Stephen M Hahn, Andy J Minn, E John Wherry, Robert H Vonderheide
BACKGROUND: We conducted a phase I trial evaluating pembrolizumab+hypofractionated radiotherapy (HFRT) for patients with metastatic cancers. METHODS: There were two strata (12 patients each): (i) NSCLC/melanoma progressing on prior anti-PD-1 therapy, (ii) other cancer types; anti-PD-1-naive. Patients received 6 cycles of pembrolizumab, starting 1 week before HFRT. Patients had ≥2 lesions; only one was irradiated (8 Gy × 3 for first half; 17 Gy × 1 for second half in each stratum) and the other(s) followed for response...
October 15, 2018: British Journal of Cancer
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