![]() ![]() Surrounded by friends who know little of his time travel experiences, Okabe spends his days trying to forget the horrors of his adventures alone. Depressed and traumatized after failing to rescue his friend Makise Kurisu, he has decided to forsake his mad scientist alter ego and live as an ordinary college student. The eccentric, self-proclaimed mad scientist Rintarou Okabe has become a shell of his former self. ![]() Thus the two otaku start dating, and their adorably awkward romance begins. Blown away by the proposal, Narumi agrees immediately. He makes a solemn promise to always be there for her, to support her, and to help her farm for rare drops in Monster Hunter. After Narumi complains about her previous boyfriend breaking up with her because he refused to date a fujoshi, Hirotaka suggests that she try dating a fellow otaku, specifically himself. Later that night, the pair go out for drinks so that they can catch up after all the years apart. Luckily for her, the only witnesses-Hanako Koyanagi and Tarou Kabakura-are otaku as well. Although she tries to keep her secret by inviting him out for drinks after work, her cover is blown when he casually asks her whether or not she will be attending the upcoming Summer Comiket. Her plan goes instantly awry, though, when she runs into Hirotaka Nifuji, an old friend from middle school. As she races to catch her train, she makes a promise to herself that none of her coworkers will find out about her dark secret: that she is an otaku and a fujoshi. Epub 2019 Apr 24.Having slept through all four of her alarms, the energetic Narumi Momose finds herself running late for her first day of work at a new office. Potential mechanisms of target-independent uptake and toxicity of antibody-drug conjugates. Mahalingaiah P.K., Ciurlionis R., Durbin K.R., Yeager R.L., Philip B.K., Bawa B., et al. Antibody conjugate therapeutics: challenges and potential. Tumor localization of radiolabeled antibodies against carcinoembryonic antigen in patients with carcinoma: a critical evaluation. ![]() Mach J.P., Carrel S., Forni M., Ritschard J., Donath A., Alberto P. Trastuzumab-DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Junttila T.T., Li G., Parsons K., Phillips G.L., Sliwkowski M.X. Paul Ehrlich's magic bullet concept: 100 years of progress. These novel TROP-2 ADCs have the potential to deliver enhanced efficacy with reduced toxicity in MBC and possibly in early stage breast cancer (EBC).Īntibody drug conjugate (ADC) Datopotamab deruxtecan Metastatic breast cancer Sacituzumab govitecan Trophoblast cell surface antigen-2 (TROP-2).Ĭopyright © 2022 The Authors. Dato-DXd is being investigated in phase III studies in metastatic TNBC and HR+/HER2- MBC. Dato-DXd demonstrated preliminary efficacy in unselected metastatic TNBC, with common AEs of low-grade nausea and stomatitis. This construct is highly stable in circulation with a longer half-life than SG, and undergoes cleavage in presence of intracellular lysosomal proteases. ![]() Datopotamab deruxtecan (Dato-DXd) is a TROP-2 ADC that differs from SG in that it has a cleavable tetrapeptide linker and a more potent topoisomerase inhibitor payload. SG also demonstrated clinical activity versus chemotherapy in a phase III trial of HR+/HER2-metastatic breast cancer (MBC) and is under evaluation in first-line metastatic and early stage TNBC as well. Common adverse events (AE) reported were neutropenia and diarrhea. There was significant improvement in progression free survival (PFS) and overall survival (OS) with SG versus chemotherapy in pretreated metastatic triple negative breast cancer (TNBC), resulting in regulatory approval. This hydrolysable linker permits intracellular and extracellular release of the membrane permeable payload enabling the "bystander effect" contributing to the efficacy of this agent. Sacituzumab govitecan (SG) is a first-in-class TROP-2-directed ADC with an anti-TROP-2 antibody conjugated to SN-38, a topoisomerase inhibitor via a hydrolysable linker. TROP-2 expression is higher in HER2-negative breast tumors (HR+/HR-) and is associated with worse survival. Trophoblast cell surface antigen 2 (TROP-2) is a transmembrane glycoprotein involved in calcium signal transduction and is expressed in multiple tumor types. Antibody drug conjugates (ADCs) combine the potent cytotoxicity of chemotherapy with the antigen -specific targeted approach of antibodies into one single molecule. ![]()
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