Impact of Different Selectivity between Soluble and Membrane-bound Forms of Carcinoembryonic Antigen (CEA) on the Target-mediated Disposition of Anti-CEA Monoclonal Antibodies.

Carcinoembryonic antigen (CEA) is a tumor-specific antigen overexpressed in multiple cancers. CEA is expressed as a membrane protein, a part of which is cleaved from the cell membrane and secreted into blood. The soluble form of CEA (sCEA) has been shown to accelerate the clearance of anti-CEA antibody, which limits the antibody distribution in the tumor.

Pharmacokinetic evaluation of liposomal nanoparticle-encapsulated nucleic acid drug: A combined study of dynamic PET imaging and LC/MS/MS analysis.

In vivo biodistribution analyses, especially in tumors, of nucleic acids delivered with nanoparticles are important to develop drug delivery technologies for medical use. We previously developed wrapsome® (WS), an ~100 nm liposomal nanoparticle that can encapsulate siRNA, and reported that WS accumulates in tumors in vivo and inhibits their growth by an enhanced permeability and retention effect. In the present study, we evaluated the pharmacokinetics of nucleic acid-containing nanoparticles by combining dynamic positron emission tomography (PET) imaging and liquid chromatography-tandem mass spectrometry (LC/MS/MS) analysis.

Development and evaluation of a novel antibody-photon absorber conjugate reveals the possibility of photoimmunotherapy-induced vascular occlusion during treatment .

Photodynamic therapy (PDT) utilize a photosensitizing agent and light for cancer therapy. It exerts anti-cancer effect mainly by inducing vascular occlusion at the irradiated site. By controlling the irradiation area, PDT can be used in a tumor-specific manner.

Novel anticarcinoembryonic antigen antibody-drug conjugate has antitumor activity in the existence of soluble antigen.

Carcinoembryonic antigen (CEA) is a classic tumor-specific antigen that is overexpressed in several cancers, including gastric cancer. Although some anti-CEA antibodies have been tested, to the best of our knowledge, there are currently no clinically approved anti-CEA antibody therapies. Because of this, we have created the novel anti-CEA antibody, 15-1-32, which exhibits stronger binding to membrane-bound CEA on cancer cells than existing anti-CEA antibodies.

One-Step Conjugation Method for Site-Specific Antibody-Drug Conjugates through Reactive Cysteine-Engineered Antibodies.

Engineered cysteine residues are particularly convenient for site-specific conjugation of antibody-drug conjugates (ADC), because no cell engineering and additives are required. Usually, unpaired cysteine residues form mixed disulfides during fermentation in Chinese hamster ovarian (CHO) cells; therefore, additional reduction and oxidization steps are required prior to conjugation. In this study, we prepared light chain (Lc)-Q124C variants in IgG and examined the conjugation efficiency.

Identification of multidrug and toxin extrusion (MATE1 and MATE2-K) variants with complete loss of transport activity.

H(+)/organic cation antiporters (multidrug and toxin extrusion: MATE1 and MATE2-K) play important roles in the renal tubular secretion of cationic drugs. We have recently identified a regulatory single nucleotide polymorphism (SNP) of the MATE1 gene (-32G>A). There is no other information about SNPs of the MATE gene.