Anti-PD-1 monoclonal antibody MEDI0680 in a phase I study of patients with advanced solid malignancies

ConclusionsMEDI0680 induced peripheral T-cell proliferation and increased plasma IFN γ and associated chemokines regardless of clinical response. CD8+ T-cell tumor infiltration and tumoral gene expression ofIFNG, CD8A,CXCL9, and granzyme K (GZMK) were also increased following MEDI0680 administration.Trial registrationNCT02013804; date of registration December 12, 2013.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research

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ConclusionsPD-1 inhibitors are now widely used in a multitude of cancer types including melanoma, advanced non-small cell lung cancer, metastatic renal cell carcinoma, and Hodgkin lymphoma amongst others. While these agents are often well tolerated, they are associated with a unique profile of immune-related toxicities that can cause significant morbidity and mortality. Education of both patients and healthcare providers is essential for diagnosis and treatment of these adverse events early in their course. This case highlights the uncommon but potentially serious PD-1-associated toxicity of myopathy and rhabdomyolysis alo...
Source: Experimental Hematology and Oncology - Category: Cancer & Oncology Source Type: research
Administration of interleukin (IL)-2 has led to a durable response in patients with advanced renal cancer and melanoma but is restricted for clinical application because of adverse effects, including the vascular leak syndrome (VLS). VLS is associated with increased circulating levels of the Tie2 antagonist ligand, angiopoietin 2, and decreased Tie2 receptor phosphorylation and downstream signaling in endothelial cells (ECs). Given that vascular endothelial protein tyrosine phosphatase (VE-PTP) is a specific membrane phosphatase in ECs that dephosphorylates Tie2, the effects of targeting VE-PTP by a selective inhibitor AKB...
Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Basic Studies Source Type: research
Authors: Ingles Garces AH, Au L, Mason R, Thomas J, Larkin J Abstract Introduction: Immunotherapy has revolutionised the treatment of cancer. Given this growing success, at the same time, there are significant limitations and unanswered questions concerning response rates, duration of therapy, why some patients respond and others do not, and if combining different immune-agents would overcome this lack of response, increase the chance of success and postpone acquired resistance. Areas covered: The comprehension of how to properly modulate the immune pathways, the molecular and the immunological bases of the disease...
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research
(Johns Hopkins Medicine) A research team led by experts at the Bloomberg~Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center reports favorable five-year survival rates from the first multidose clinical trial of the immunotherapy drug nivolumab (anti-PD-1) as a treatment for patients whose previous therapies failed to stem their advanced melanoma, renal cell carcinoma (RCC) or non-small-cell lung cancer (NSCLC).
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
AbstractBackgroundNivolumab is administered in a weight-based or fixed-flat dosing regimen. For patients with non-small cell lung cancer (NSCLC), a potential exposure-response relationship has recently been reported and may argue against the current dosing strategies. The primary objectives were to determine nivolumab pharmacokinetics (PK) and to assess the relationship between drug clearance and clinical outcome in NSCLC, melanoma, and renal cell cancer (RCC).MethodsIn this prospective observational cohort study, individual estimates of nivolumab clearance and the impact of baseline covariates were determined using a popu...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Publication date: Available online 11 July 2019Source: American Journal of Kidney DiseasesAuthor(s): Roman Shingarev, Ilya G. GlezermanImmunologic control of malignancy has long been recognized as an important determinant of disease progression. Recent advances in immunology have led to the focus on several mechanisms that can be targeted to achieve tumor suppression. In particular, checkpoint inhibition has evolved in less than a decade to become one of the most important strategies in cancer therapy, with a meaningful improvement in patient survival. Six agents have been approved for clinical use to date and many more ar...
Source: American Journal of Kidney Diseases - Category: Urology & Nephrology Source Type: research
CONCLUSION: This large, multivariate analysis demonstrated that antibiotic use is an independent negative predictor of PFS and OS in patients with advanced cancer treated with ICIs. This study highlighted worse treatment outcomes from patients with cumulative (multiple or prolonged courses) antibiotic use, which warrants further investigation and may subsequently inform clinical practice guidelines advocating careful use of antibiotics. IMPLICATIONS FOR PRACTICE: Antibiotic use is negatively associated with treatment outcomes of immune checkpoint inhibitors (ICI) in advanced cancer. Cumulative antibiotic use is associ...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
This review focuses on what is the biological basis of esophageal cancer for immunotherapy, how to screen out the patients who can benefit from immunotherapy, and whether the toxic side effects of immunotherapy are manageable. AbstractConsidering the benefits of immunotherapy in advanced melanoma, non –small cell lung cancer, renal cell carcinoma, bladder cancers, and refractory Hodgkin lymphoma, we begin to consider whether immunotherapy is effective for esophageal cancer, which is extremely malignant and has a poor prognosis. There are a large number of clinical trials to study the applicatio n of immunotherapy suc...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: REVIEW Source Type: research
AbstractBackground.Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors.Materials and Methods.Consecutive patients with advanced cancer, treated with anti‐programmed death‐1 (PD‐1) agents, were evaluated according to the presence of pre‐existing AIDs. The incidence of immune‐related adverse events (irAEs) and clinical outcomes were compared among subgroups.Results.A total of 751 patients were enrolled; median age was 69 years. Primary tumors were as follows: non‐small cell lung cancer, 492 (65.5%); melanoma, 159 (21.2%);...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Precision Medicine Clinic: Molecular Tumor Board Immuno ‐ Oncology Source Type: research
AbstractCancer cells can escape the immune system by different mechanisms. The evasion of cancer cells from immune surveillance is prevented by immune checkpoint inhibitors, allowing the patient ’s own immune system to attack their cancer. Immune checkpoint inhibitors have shown improvement in overall survival for melanoma, lung cancer and renal cell carcinoma in clinical trials. Unfortunately, not all patients respond to this therapy.In cancer management, percutaneous ablation techniques are well established for both cure and local control of many tumour types. Cryoablation of the tumour tissue results in cell destr...
Source: Insights into Imaging - Category: Radiology Source Type: research
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