Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma.

Background: Tebentafusp, a T-cell receptor-bispecific molecule that targets glycoprotein 100 and CD3, is approved for adult patients who are positive for HLA-A*02:01 and have unresectable or metastatic uveal melanoma. The primary analysis in the present phase 3 trial supported a long-term survival benefit associated with the drug.

Methods: We report the 3-year efficacy and safety results from our open-label, phase 3 trial in which HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma were randomly assigned in a 2:1 ratio to receive tebentafusp (tebentafusp group) or the investigator's choice of therapy with pembrolizumab, ipilimumab, or dacarbazine (control group), with randomization stratified according to the lactate dehydrogenase level.

Differences in radiation-induced heart dysfunction in male versus female rats.

Purpose: Radiation therapy remains part of the standard of care for breast, lung, and esophageal cancers. While radiotherapy improves local control and survival, radiation-induced heart dysfunction is a common side effect of thoracic radiotherapy. Cardiovascular dysfunction can also result from non-therapeutic total body radiation exposures.

Development of Lymphopenia during Therapy with Immune Checkpoint Inhibitors Is Associated with Poor Outcome in Metastatic Cutaneous Melanoma.

Predictive markers for immune checkpoint inhibitor (ICI) therapy are needed. Thus, baseline blood counts have been investigated as biomarkers, showing that lymphopenia at the start of therapy with (ICI) is associated with a worse outcome in metastatic melanoma. We investigated the relationship between the occurrence of lymphopenia under ICI and disease outcome.

A benchmark for neural network robustness in skin cancer classification.

Background: One prominent application for deep learning-based classifiers is skin cancer classification on dermoscopic images. However, classifier evaluation is often limited to holdout data which can mask common shortcomings such as susceptibility to confounding factors. To increase clinical applicability, it is necessary to thoroughly evaluate such classifiers on out-of-distribution (OOD) data.

Immune Checkpoint Blockade for Metastatic Uveal Melanoma: Patterns of Response and Survival According to the Presence of Hepatic and Extrahepatic Metastasis.

Background: Since there is no standardized and effective treatment for advanced uveal melanoma (UM), the prognosis is dismal once metastases develop. Due to the availability of immune checkpoint blockade (ICB) in the real-world setting, the prognosis of metastatic UM has improved. However, it is unclear how the presence of hepatic and extrahepatic metastasis impacts the response and survival after ICB.

Hematological immune related adverse events after treatment with immune checkpoint inhibitors.

Introduction: With the increasing use of checkpoint inhibitors, rare immune-related adverse events (irAE) are being identified. Haematological irAE (hem-irAE) are difficult to treat and have shown high mortality rates. In order to improve side-effect management for these potentially life-threatening events, we analysed frequency, severity and outcomes.

Treatment Monitoring of Immunotherapy and Targeted Therapy Using F-FET PET in Patients with Melanoma and Lung Cancer Brain Metastases: Initial Experiences.

We investigated the value of -(2-F-fluoroethyl)-l-tyrosine (F-FET) PET for treatment monitoring of immune checkpoint inhibition (ICI) or targeted therapy (TT) alone or in combination with radiotherapy in patients with brain metastasis (BM) since contrast-enhanced MRI often remains inconclusive. We retrospectively identified 40 patients with 107 BMs secondary to melanoma ( = 29 with 75 BMs) or non-small cell lung cancer ( = 11 with 32 BMs) treated with ICI or TT who had F-FET PET ( = 60 scans) for treatment monitoring from 2015 to 2019. Most patients ( = 37; 92.

Acquired Immunity Is Not Essential for Radiation-Induced Heart Dysfunction but Exerts a Complex Impact on Injury.

While radiation therapy (RT) can improve cancer outcomes, it can lead to radiation-induced heart dysfunction (RIHD) in patients with thoracic tumors. This study examines the role of adaptive immune cells in RIHD. In Salt-Sensitive (SS) rats, image-guided whole-heart RT increased cardiac T-cell infiltration.

The efficacy of re-challenge with BRAF inhibitors after previous progression to BRAF inhibitors in melanoma: A retrospective multicenter study.

BRAF and MEK inhibition is efficient in patients with BRAF V600-mutated metastatic melanoma, but due to acquired resistance the duration of response (DoR) is often only short-lived. In this retrospective multicenter study with 60 patients suffering from inoperable or metastatic melanoma we evaluated the efficacy of re-challenge with a BRAF inhibitor (BRAF2) with or without MEK-inhibition after progressive disease upon previous treatment with a BRAF inhibitor (BRAF1) with or without MEK inhibition. Treatment with BRAF1 led to a disease control rate (DCR) of 90% with 12% complete responses (CR), 58% partial responses (PR) and 20% stable diseases (SD), the median progression-free survival (PFS) was 9.

Ipilimumab in metastatic melanoma patients with pre-existing autoimmune disorders.

Background: Ipilimumab and programmed death (PD) 1-antibodies are effective treatment options in metastatic melanoma. The safety and efficacy of ipilimumab in patients with pre-existing autoimmune disorders (AD) has only been evaluated in a selected number of patients.

Methods: We performed a retrospective analysis in 14 German skin cancer centers for patients with metastatic melanoma and pre-existing AD treated with ipilimumab.

Nucleic acid-based polymers effective against hepatitis B Virus infection in patients don't harbor immunostimulatory properties in primary isolated liver cells.

Nucleic acid polymers (NAPs) block the release of subviral particles from hepatocytes, a mechanism consistent with their antiviral activity against hepatitis B virus (HBV) in patients. Analysis of immunostimulatory properties of NAPs were conducted with several NAP species: REP 2006, the prototypic degenerate NAP [dN], containing TLR9-stimulatory CpG; REP 2055 a clinically active NAP with a sequence [dAdC] devoid of CpG content; REP 2139 (also clinically active) and REP 2165 (REP 2055 analogues further rendered immunologically inactive by replacing cytidine with 5-methylcytidine and incorporating 2'-O methylation of riboses). These analyses revealed pro-inflammatory responses in human peripheral blood mononuclear cells with REP 2006 and with REP 2139 and REP 2165 only at high dose but displayed no significant antiviral activity.

Depression and protective factors of mental health in people with hepatitis C: a questionnaire survey.

Background: Most studies investigating the effects of chronic hepatitis C (HCV) infection on the central nervous system have focused on cognitive impairment or on the health-related quality of life, but only few on depression.

Objectives: This study investigated depression in HCV-infected people. Sense of coherence and social support were surveyed as protective factors of mental health.

A new in vitro model for studying human T cell differentiation: T(H1)/T(H2) induction following activation by superantigens.

A new T(H1)/T(H2) in vitro model for mechanistic studies and drug screening in human T cells was established working with ficoll-separated PBMCs or elutriated lymphocytes cultured in serum-free medium. Human T cells could be kept viable and reactive in this medium for several months. In this model, superantigens (SAs) were used to activate exclusively those T cell clones which were known to express specifically SA-binding Vbeta-chains of the T cell receptor.

Studies on the carbohydrate moieties of the timothy grass pollen allergen Phl p I.

Timothy grass pollen was investigated in order to determine the carbohydrate moieties of its major grass group I (Phl p I) and to study its impact on allergenicity. Based on computer calculations one N-glycosylation site was deduced from the cDNA data of Phl p I. After two-dimensional polyacrylamide gel electrophoresis, followed by blotting of pollen extract and by use of the monoclonal antibody IG 12 we identified at least six isoallergens of Phl p I with the main spots at a molecular mass of 35-37 kDa and a pI range of 6.

Conventional isoelectric focusing does not dissociate immune complexes.

Contrary to some reports, isoelectric focusing (IEF) is unable to dissociate immune complexes (IC) into their constituent components. Six model IC systems prepared at various antigen/antibody ratios were readily dissociated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), but not by conventional IEF, independently of several modifications of the running conditions. IC preformed in situ in the IEF gel were not disrupted by subsequent electrophoresis.