PVRIG is Expressed on Stem-Like T Cells in Dendritic Cell-Rich Niches in Tumors and Its Blockade May Induce Immune Infiltration in Non-Inflamed Tumors.

Cancers that are poorly immune infiltrated pose a substantial challenge, with current immunotherapies yielding limited clinical success. Stem-like memory T cells (TSCM) have been identified as a subgroup of T cells that possess strong proliferative capacity and that can expand and differentiate following interactions with dendritic cells (DCs). In this study, we explored the pattern of expression of a recently discovered inhibitory receptor poliovirus receptor-related immunoglobulin domain protein (PVRIG) and its ligand, poliovirus receptor-related ligand 2 (PVRL2), in the human tumor microenvironment.

Unleashing Natural IL18 Activity Using an Anti-IL18BP Blocker Induces Potent Immune Stimulation and Antitumor Effects.

Recombinant cytokines have limited anticancer efficacy mostly due to a narrow therapeutic window and systemic adverse effects. IL18 is an inflammasome-induced proinflammatory cytokine, which enhances T- and NK-cell activity and stimulates IFNγ production. The activity of IL18 is naturally blocked by a high-affinity endogenous binding protein (IL18BP).

10th antibody industrial symposium: new developments in antibody and adoptive cell therapies.

The annual "Antibody Industrial Symposium", co-organized by LabEx MAbImprove and MabDesign, held its 10th anniversary edition in Montpellier, France, on June 28-29, 2022. The meeting focused on new results and concepts in antibody engineering (naked, mono- or multi-specific, conjugated to drugs or radioelements) and also on new cell-based therapies, such as chimeric antigenic receptor (CAR)-T cells. The symposium, which brought together scientists from academia and industry, also addressed issues concerning the production of these molecules and cells, and the necessary steps to ensure a strong intellectual property protection of these new molecules and approaches.

Randomized, double-blind trial of F14512, a polyamine-vectorized anticancer drug, compared with etoposide phosphate, in dogs with naturally occurring lymphoma.

F14512 is an epipodophyllotoxin derivative from etoposide, combined with a spermine moiety introduced as a cell delivery vector. The objective of this study was to compare the safety and antitumor activity of F14512 and etoposide phosphate in dogs with spontaneous non-Hodgkin lymphoma (NHL) and to investigate the potential benefit of F14512 in P-glycoprotein (Pgp) overexpressing lymphomas. Forty-eight client-owned dogs with intermediate to high-grade NHL were enrolled into a randomized, double-blind trial of F14512 etoposide phosphate.

A randomised, multicentre open-label phase II study to evaluate the efficacy, tolerability and pharmacokinetics of oral vinorelbine plus cisplatin versus intravenous vinorelbine plus cisplatin in Chinese patients with chemotherapy-naive unresectable or metastatic non-small cell lung cancer.

Background: A phase II study to evaluate the efficacy, tolerability and pharmacokinetics of oral or intravenous vinorelbine (VRL) plus cisplatin (CDDP) in Chinese patients with non-small cell lung cancer (NSCLC).

Methods: One hundred and thirty-one patients were randomised to oral VRL 60 mg/m (arm A) or intravenous VRL 25 mg/m (arm B) on days 1 and 8, plus CDDP 80 mg/m on day 1 (both arms). VRL was increased to 80 mg/m (arm A) or 30 mg/m (arm B) in cycles 2-4 in the absence of toxicity.

Tumor Cells Hijack Macrophage-Produced Complement C1q to Promote Tumor Growth.

Clear-cell renal cell carcinoma (ccRCC) possesses an unmet medical need, particularly at the metastatic stage, when surgery is ineffective. Complement is a key factor in tissue inflammation, favoring cancer progression through the production of complement component 5a (C5a). However, the activation pathways that generate C5a in tumors remain obscure.

Effect of ethnicity on vinorelbine pharmacokinetics: a population pharmacokinetics analysis.

Background: Pharmacokinetics of vinorelbine is mainly known from studies conducted in European patients. Interethnic differences in drug disposition may, however, induce interethnic variation in drug exposure. This paper aimed to evaluate the effect of ethnicity on the bioavailability and clearance of oral and intravenous vinorelbine.

Phase I dose-escalation study of F50067, a humanized anti-CXCR4 monoclonal antibody alone and in combination with lenalidomide and low-dose dexamethasone, in relapsed or refractory multiple myeloma.

Purpose: Multiple myeloma (MM) remains an incurable disease as tumor cells ultimately resist to all available drugs. Homing of tumor cells to the bone marrow microenvironment, involving especially the CXCR4/SDF-1 axis, allows them to survive, proliferate and resist to therapy. F50067, a humanized anti-CXCR4 IgG1 antibody, has promising preclinical activity in MM.

Better characterization of vinflunine pharmacokinetics variability and exposure/toxicity relationship to improve its use: Analyses from 18 trials.

Aims: Vinflunine is a novel tubulin-targeted inhibitor indicated as a single agent for the treatment of bladder cancers after failure of prior platinum-based therapy. Its pharmacokinetics (PK) and pharmacodynamics (PD) have been independently characterized through several phase I and phase II studies. However, no global pharmacometric analysis had been conducted as yet.

Metronomic treatment of advanced non-small-cell lung cancer with daily oral vinorelbine - a Phase I trial.

Micro-abstract: In a Phase I dose-finding study of metronomic daily oral vinorelbine in advanced non-small-cell lung cancer, a recommended dose was established for this therapeutic approach. In addition, this trial revealed promising efficacy data and an acceptable tolerability profile. The observed vinorelbine blood concentrations suggest continuous anti-angiogenic coverage.

F14512, a polyamine-vectorized inhibitor of topoisomerase II, exhibits a marked anti-tumor activity in ovarian cancer.

Epithelial ovarian cancer is the fourth cause of death among cancer-bearing women and frequently associated with carboplatin resistance, underlining the need for more efficient and targeted therapies. F14512 is an epipodophylotoxin-core linked to a spermine chain which enters cells via the polyamine transport system (PTS). Here, we investigate this novel concept of vectorization in ovarian cancer.

Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma.

Purpose: F14512 is a new topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells and increases topoisomerase II poisoning. F14512 is currently in a phase I/II clinical trial in patients with acute myeloid leukemia. The aim of this study was to investigate F14512 potential in a new clinical indication.

Phase I and pharmacokinetic study of IV vinflunine in combination with carboplatin in chemonaive patients with advanced non-small cell lung cancer.

Objective: Vinflunine (VFL) (Javlor(®)), a novel fluorinated semisynthetic vinca alkaloid has shown significant antitumor activity in advanced non-small cell lung cancer (NSCLC). We propose to define the recommended dose (RD) of VFL in combination with carboplatin in advanced NSCLC patients.

Methods: This phase I and pharmacokinetic study was designed to determine the maximum tolerated dose and to establish the RD of VFL in combination with carboplatin.

Vinflunine oral pharmacokinetics and absolute bioavailability of soft and hard gelatin capsules: results of two phase I trials.

Background: Vinflunine is a new-generation microtubule inhibitor, which is currently registered in Europe and in some countries elsewhere as an intravenous formulation for the second-line treatment of transitional urothelial cell carcinoma. On the basis of favourable non-clinical results, the clinical development of an oral formulation was initiated.

Objective: The absolute oral bioavailability was investigated in patients through two consecutive trials: the first trial used soft gelatin capsules filled with solubilized vinflunine (SLCaps), while the second study investigated hard gelatin capsules containing vinflunine as a formulated powder (HPCaps).

Chronic lymphatico-venous bypass: surgical technique and aftercare in a porcine model.

We describe a chronic model of lymphatico-venous bypass in pigs with emphasis to surgical considerations, major per- and postoperative complications. A catheter (silicone or heparin coated polyurethane) was inserted in the thoracic duct of nine pigs via a right intercostal thoracotomy. A second catheter was surgically inserted in the jugular vein and the bypass was secured on the back of the animals.

Longitudinal analysis of gene expression in porcine skeletal muscle after post-injection local injury.

Purpose: The purpose of this study is to describe the time course of gene expression in a skeletal muscle local injury induced by an intramuscular (IM) injection, and to compare the dynamics of gene expression with pathological events.

Materials And Methods: Ten piglets received 4 IM injections of propylene glycol in the longissimus dorsi muscles 6 h, 2, 7, and 21 days before euthanasia, where control and injected muscle sites were sampled for RNA isolation and microscopic examination. The hybridization of nylon cDNA microarrays was carried out with radioactive probes obtained from the muscle RNA.

Plasma pharmacokinetics of alfaxalone in dogs after an intravenous bolus of Alfaxan-CD RTU.

Objective: To determine the pharmacokinetic parameters of alfaxalone in dogs after the intravenous (IV) administration of clinical and supra-clinical doses of a 2-hydroxypropyl-beta-cyclodextrin (HPCD) alfaxalone formulation (Alfaxan-CD RTU).

Experimental Design: Prospective two-period crossover design. Animals Eight (four male and four female) young adult healthy Beagle dogs.

Acute changes in muscle blood flow and concomitant muscle damage after an intramuscular administration.

Purpose: The intramuscular route (IM) is widely used but commonly induces injection site muscle damage. This study investigates the hemodynamic changes in an acute lesion induced by the IM administration of propylene glycol (PG) in rabbits.

Methods: Control groups received 1, 2, or 3 ml of PG (IM).