Bispecific Antibody Approach for Improved Melanoma-Selective PD-L1 Immune Checkpoint Blockade

Reactivation of functionally-impaired anticancer T cells by programmed cell death protein 1 (PD-1) and programmed cell death receptor ligand-1 (PD-L1) –blocking antibodies shows prominent therapeutic benefit in advanced melanoma and patients with non–small cell lung cancer. However, current PD-L1–blocking antibodies lack intrinsic tumor selectivity. Therefore, efficacy may be reduced resulting from on-target and off-tumor binding to PD-L1– expressing normal cells. This may lead to indiscriminate activation of antigen-experienced T cells, including those implicated in autoimmune-related adverse events.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Original Article Source Type: research

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Clara Degos1, Mellie Heinemann2, Julien Barrou2, Nicolas Boucherit1, Eric Lambaudie2, Ariel Savina3†, Laurent Gorvel1* and Daniel Olive1* 1Tumor Immunology Team, IBISA Immunomonitoring Platform, Cancer Research Center of Marseillle, INSERM U1068, CNRS U7258, Institut Paoli-Calmettes, Aix-Marseille University, Marseille, France 2Department of Surgical Oncology 2, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Aix-Marseille University, Marseille, France 3Institut Roche, Boulogne Billancourt, France Endometrial Cancer is the most common cancer in the female genital tract in developed countries, and with its ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Personalized Dendritic Cell Vaccines—Recent Breakthroughs and Encouraging Clinical Results Beatris Mastelic-Gavillet, Klara Balint, Caroline Boudousquie, Philippe O. Gannon and Lana E. Kandalaft* Department of Oncology, Center for Experimental Therapeutics, Ludwig Center for Cancer Research, University of Lausanne, Lausanne, Switzerland With the advent of combined immunotherapies, personalized dendritic cell (DC)-based vaccination could integrate the current standard of care for the treatment of a large variety of tumors. Due to their proficiency at antigen presentation, DC are key coordinators of the innate...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
AbstractPurpose of ReviewInterleukin-10 (IL-10) is a cytokine with anti-inflammatory properties, which induces activation and proliferation of antigen-activated intratumoral CD8+ T cells. This review discusses the evolution of pegylated IL-10 (pegilodecakin) from preclinical investigation through first-in-human studies in oncology.Recent FindingsPegilodecakin was evaluated across multiple advanced solid tumors in a large phase 1/1b trial alone and in combination with chemotherapy or anti-PD-1 antibodies. Pegilodecakin monotherapy had immunologic and clinical activity in renal cell carcinoma (RCC) and uveal melanoma. In com...
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research
(Thomas Jefferson University) Scientists from the Sidney Kimmel Cancer Center (SKCC) at Jefferson Health will be presenting research and leading discussions on various topics, including metastatic uveal melanoma, genetic counseling in men, immunotherapy in early stage lung cancer and solid tumors, quality of life among patients receiving treatment for T cell lymphoma and updates on the Cancer Moonshot during the Biden Cancer Initiative Colloquium at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, being held June 1-5 in Chicago.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
CONCLUSION: Modern diagnostic and therapeutic concepts for intraocular tumors can only be implemented through the close interdisciplinary collaboration of ophthal - mologists, oncologists, radiologists, radiotherapists, pathologists, and human geneticists. PMID: 29510820 [PubMed - in process]
Source: Deutsches Arzteblatt International - Category: General Medicine Tags: Dtsch Arztebl Int Source Type: research
Abstract Reirradiation (reRT) for locoregional recurrences poses unique challenges and risks; re-treatment using proton beam radiotherapy (PBT) could prove advantageous. Assessing clinical outcomes and toxicity profiles, this systematic review comprehensively evaluated available evidence regarding PBT reRT. Fourteen original investigations across central nervous system (CNS) (n=6), head/neck (H&N) (n=4), lung (n=2), and gastrointestinal (n=2) malignancies were analyzed. PBT for recurrent uveal melanoma achieved 5-year eye retention of 55%; for chordomas, reRT afforded a 2-year local control and overall survival (O...
Source: Radiotherapy and Oncology : journal of the European Society for Therapeutic Radiology and Oncology - Category: Radiology Authors: Tags: Radiother Oncol Source Type: research
Abstract Familial risks of breast cancer (BC) are well established but whether BC clusters with other, i.e. discordant, cancers is less certain but of interest for the identification of common genetic and possible environmental factors contributing to a general cancer susceptibility. We apply a novel approach to search for familial associations of BC with other (discordant) cancers based on the Swedish Family‐Cancer Database. Relative risks (RRs) were calculated for BC in families with increasing numbers of patients with discordant cancer X, and conversely, familial RRs for cancer X in families with increasing numbers of...
Source: International Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Article Source Type: research
Abstract: Solitary choroidal metastasis as an initial presentation of lung cancer is rare. A 67-year-old woman who initially presented with a 3-month history of blurred vision in the right eye was suggestive of choroidal melanoma on MRI. Preoperatively, a pulmonary mass was found on x-ray. She was referred for an FDG PET/CT imaging, which revealed a choroidal lesion with minimal FDG uptake in right eye and increased FDG activity in the known lung mass. A pathological diagnosis of metastatic lung adenocarcinoma was made after enucleation of the right eyeball.
Source: Clinical Nuclear Medicine - Category: Nuclear Medicine Tags: Interesting Images Source Type: research
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