The Nonclinical Safety Assessment of a Novel Anti-CEACAM5 Antibody Exatecan Conjugate Predicts a Low Risk for Interstitial Lung Disease (ILD) in Patients-The Putative Mechanism Behind ILD.

The therapeutic window of antibody drug-conjugates (ADC) remains challenging due to safety issues such as interstitial lung disease (ILD) observed with specific deruxtecan-based ADCs. To avoid ILD, we designed M9140 by conjugating the maleimide-containing hydrophilic β-glucuronide linker to exatecan and our anti-CEACAM5 (CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 5) specific antibody. Following repeated iv-infusion at 3 to 30 mg/kg of M9140 every 3 weeks, the pathological findings obtained in cynomolgus monkeys were confined to gastrointestinal and hematolymphoid tissues and resembled the toxicity of exatecan.

Canopy Architectural Characteristics of Ten New Olive ( L.) Genotypes and Their Potential for Cultivation in Super-High-Density Orchards.

In recent years, there has been growing interest in olive genotypes ( L.) suitable for super-high-density (SHD > 1200 trees/hectare) orchards. To date, only a few cultivars are considered fitting for such cultivation system.

Dodine an effective alternative to copper for controlling , the causal agent of pea-cock eye disease, in highly infected olive trees.

A trial was carried out in central Italy in an olive orchard of cultivar Moraiolo, highly infected by . The aim of the investigation was to evaluate the effects of autumn and spring applications of copper oxychloride or dodine to control the disease. Non treated trees were used as the control.

Cultivar ideotype for intensive olive orchards: plant vigor, biomass partitioning, tree architecture and fruiting characteristics.

In order to achieve higher and earlier yield, modern olive orchards are increasingly intensified, with tree densities up to > 1500 trees hectare. With increasing tree densities, individual-tree canopy volume must be proportionally reduced. Not all cultivars are adaptable to high and very high orchard densities, because of excessive vigor and/or insufficient bearing when the canopy is pruned to a small volume.

Avelumab internalization by human circulating immune cells is mediated by both Fc gamma receptor and PD-L1 binding.

Avelumab is an IgG1 anti-programmed death ligand 1 (anti-PD-L1) monoclonal antibody that has been approved as a monotherapy for metastatic Merkel cell carcinoma and advanced urothelial carcinoma, and in combination with axitinib for advanced renal cell carcinoma. Avelumab is cleared faster and has a shorter half-life than other anti-PD-L1 antibodies, such as atezolizumab and durvalumab, but the mechanisms underlying these differences are unknown. IgG antibodies can be cleared through receptor-mediated endocytosis after binding of the antibody Fab region to target proteins, or via Fcγ receptor (FcγR)-mediated endocytosis.

Effect of Conjugation Site and Technique on the Stability and Pharmacokinetics of Antibody-Drug Conjugates.

Appropriate selection of conjugation sites and conjugation technologies is now widely accepted as crucial for the success of antibody-drug conjugates (ADCs). Herein, we present ADCs conjugated by different conjugation methods to different conjugation positions being systematically characterized by multiple in vitro assays as well as in vivo pharmacokinetic (PK) analyses in transgenic Tg276 mice. Conjugation to cysteines, genetically introduced at positions N325, L328, S239, D265, and S442, was compared to enzymatic conjugation via microbial transglutaminase (mTG) either to C-terminal light (LC) or heavy chain (HC) recognition motifs or to endogenous position Q295 of a native antibody.

Effects of cultivar, fruit presence and tree age on whole-plant dry matter partitioning in young olive trees.

This study investigated the effects of cultivar, fruit presence and tree age on whole-plant partitioning of dry matter and energy equivalents (i.e., glucose equivalents).

A novel monovalent FGFR1 antagonist: Preclinical safety profiles in rodents and non-human primates.

Blocking Fibroblast Growth Factor Receptor 1 (FGFR1) is an attractive therapeutic option for treatment of cancer subtypes with amplification and over-expression of FGFR1. Selective targeting of FGFR1 can be achieved using an antibody-based approach, as small molecule inhibitors may not discriminate between FGFR1, 2, 3 and 4 due to their highly homologous kinase domain. However, development of classical bivalent FGFR1 directed antibodies has failed due to non-tolerated body weight decreases in preclinical species.

Identification and characterization of M6903, an antagonistic anti-TIM-3 monoclonal antibody.

T cell immunoglobulin and mucin domain-3 (TIM-3) is an immune checkpoint that regulates normal immune responses but can be exploited by tumor cells to evade immune surveillance. TIM-3 is primarily expressed on immune cells, particularly on dysfunctional and exhausted T cells, and engagement of TIM-3 with its ligands promotes TIM-3-mediated T cell inhibition. Antagonistic ligand-blocking anti-TIM-3 antibodies have the potential to abrogate T cell inhibition, activate antigen-specific T cells, and enhance anti-tumor immunity.

Resource investments in reproductive growth proportionately limit investments in whole-tree vegetative growth in young olive trees with varying crop loads.

It has long been debated whether tree growth is source limited, or whether photosynthesis is adjusted to the actual sink demand, directly regulated by internal and environmental factors. Many studies support both possibilities, but no studies have provided quantitative data at the whole-tree level, across different cultivars and fruit load treatments. This study investigated the effect of different levels of reproductive growth on whole-tree biomass growth across two olive cultivars with different growth rates (i.

Fruit production and branching density affect shoot and whole-tree wood to leaf biomass ratio in olive.

The amount of shoot stem (i.e., woody part of the shoot) dry matter per unit shoot leaf dry matter (i.

Phosphorylation of phosphoenolpyruvate carboxykinase (PEPCK) and phosphoenolpyruvate carboxylase (PEPC) in the flesh of fruits.

This study determined whether phosphoenolpyruvate carboxykinase (PEPCK) and phosphoenolpyruvate carboxylase (PEPC) are phosphorylated in the flesh of a range of fruits. This was done by incubating fruit flesh with P[P] (where P[P] = PO), then PEPCK and PEPC were immunoprecipitated from extracts using specific antisera. The incorporation of P[P] into these enzymes was then determined by autoradiography of SDS-PAGE gels.

Phosphoenolpyruvate carboxykinase, pyruvate orthophosphate dikinase and isocitrate lyase in both tomato fruits and leaves, and in the flesh of peach and some other fruits.

In this study the occurrence of a number of enzymes involved in gluconeogenesis was investigated in both tomato fruits and leaves during their development and senescence and in some other fruits. The enzymes studied were phosphoenolpyruvate carboxykinase (PEPCK), pyruvate orthophosphate dikinase (PPDK) and glyoxysomal isocitrate lyase (ICL). PPDK was detected in the ripe flesh of tomato, and much smaller amounts were detected in the flesh of both peach and pepper, whereas it was not detected (not present or at very low abundance) in the other fruits which were investigated (apricot, aubergine, blackberry, blueberry, cherry, grape, plum, raspberry and red current).

Effect of agronomical practices on carpology, fruit and oil composition, and oil sensory properties, in olive (Olea europaea L.).

We examined whether some agronomical practices (i.e. organic vs.

Tissue size and cell number in the olive (Olea europaea) ovary determine tissue growth and partitioning in the fruit.

The relationship between tissue size and cell number in the ovary and tissue size in the fruit, was studied in eight olive (Olea europaea L.) cultivars with different fruit and ovary size. All tissues in the ovary increased in size with increasing ovary size.