Izalontamab

SI-B001 is a new EGFR/HER3 bi-specific antibody showing encouraging anti-tumor efficacy in the preclinical studies and was ready for further clinical research. To help with the dose design, human pharmacokinetics (PK) and clinical effective doses of SI-B001 were predicted by PK and PK/PD modeling and simulation. A Michaels-Menten (M-M) PK model was first used to describe the PK of SI-B001 in cynomolgus monkeys, whose parameters were allometrically scaled to humans for the simulation of human PK profiles. Besides, the anti-tumor efficacy of SI-B001 on different xenografts in tumor-bearing mice was quantitatively described by PK/PD models. The clinical effective doses were predicted by comparing the effective exposure (AUCs) in mice with simulated human AUCs. The clinical effective doses of SI-B001 were predicted to be over 16 mg/kg, 5-7 mg/kg or 5-6 mg/kg per week for colon cancer, head and neck cancer or esophageal cancer, respectively, which may help with the optimization of dose escalation schemes and the selection of indications for SI-B001.

Direct discharge of untreated industrial waste water in water bodies and then irrigation from these sources has increased trace metals contamination in paddy fields of southern China. Among trace metals, cadmium (Cd) and lead (Pb) are classified as most harmful contaminants in farmland to many organisms including plants, animals and humans. Rice is a staple food which is consumed by half population of the world; due to longer growth period it can easily absorb and accumulate the trace metals from soil. The objective of study was to check the efficacy of Se and Si NPs (nanoparticles) alone or in combination on metals accumulation and Se-fortified rice (Oryzasativa L.) production as their efficiency remained untested. Alone as well as combined application of Se- and Si-NPs (5, 10 and 20 mg L^-1) was achieved along with CK. All the treatments significantly reduced the Cd and Pb contents in brown rice, except CK, Se3, Si1 and Se1Si3. Combined application of Se and Si (Se3Si2) was more effective in reducing the Cd and Pb contents by 62 and 52%, respectively. In addition, foliar application of both NPs improved the rice growth and quality by increasing the grain yield, rice biomass, and Se contents in brown rice. Highest concentration of Se (1.35 mg kg^-1) in brown rice was observed with combined application of Se- and Si-Nps (Se3Si2). Selenium speciation revealed the presence of organic species (74%) in brown rice. The combinations of different doses of Se- and Si-Nps are the main determining factor for total concentration of metals in grains. These results demonstrate that foliage supplementation of Se and Si-Nps alleviate the Cd and Pb toxicity by reducing the metals' concentration in brown rice. Additionally foliage supplementation improved the nutritional quality by reducing the phytic acid contents in rice grains.