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http://dx.doi.org/10.1200/JCO.22.02217 | DOI Listing |
Cancer Immunol Res
September 2025
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States.
Antibody-based therapies have revolutionized cancer treatment but have several limitations. These include: down-regulation of the target antigen; mutation of the target epitope; or in the case of antibody drug conjugates (ADCs), resistance to the chemotherapy warhead. Since TROP2-targeted therapy with ADCs yields responses in TROP2+ solid tumors but lacks the durability observed with other immunotherapy-based approaches, we developed novel TROP2-targeting chimeric antigen receptor (CAR) T cells as an alternative.
View Article and Find Full Text PDFJ Am Chem Soc
September 2025
Center for Chemical Glycobiology, Shanghai Key Laboratory for Antibody-Drug Conjugates with Innovative Target, State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
The ability to selectively cleave C-heteroatom bonds is critically important in chemical science, from peptide and protein synthesis to biomolecule manipulation. For example, C-heteroatom bond cleavage is widely used in fluorenylmethyloxycarbonyl/-butyl (Fmoc/Bu)-based solid-phase peptide synthesis (SPPS). Despite its usefulness, it has inextricable limitations, such as issues with hydrophobicity and side reactions, owing to the need for the use of a strong trifluoroacetic acid (TFA, a pervasive forever chemical) as the cleavage reagent.
View Article and Find Full Text PDFFront Oncol
August 2025
Department of Lung Cancer Surgery, Department of Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.
TROP2, a transmembrane glycoprotein, is overexpressed and plays pivotal roles in diverse epithelial tumors. The differential expression of TROP2 between cancer and normal tissues offers distinct advantages in developing drugs targeting it. Thus, TROP2-targeted antibody-drug conjugates (ADCs), including datopotamab deruxtecan and sacituzumab govitecan, present considerable efficacy and safety in multiple cancers.
View Article and Find Full Text PDFOncol Res
September 2025
The Breast Center, Cancer Hospital of Shantou University Medical College, Guangdong Provincial Key Laboratory of Breast Cancer Diagnosis and Treatment, Shantou, 515031, China.
Background: Breast cancer remains a leading cause of morbidity and mortality among women worldwide, with significant geographic disparities in its impact. While human epidermal growth factor receptor 2 (HER2)-targeted therapies, such as trastuzumab, have improved outcomes for HER2-positive breast cancer, challenges like therapy resistance persist, highlighting the need for novel treatments. Recent developments in antibody-drug conjugates (ADCs), particularly disitamab vedotin (RC48), show promising efficacy in targeting both HER2-positive and HER2-low expression tumors, warranting further investigation through real-world studies to assess its broader clinical applicability.
View Article and Find Full Text PDFACS Omega
September 2025
Ajinomoto Bio-Pharma Services, 11040 Roselle Street, San Diego, California 92121, United States.
Antibody-drug conjugates (ADCs) represent a transformative class of cancer therapies that combine the specificity of monoclonal antibodies with the cytotoxicity of potent drug payloads. This study presents the development and evaluation of a novel linker platform designed to enhance ADC stability and pharmacokinetics by addressing the limitations associated with traditional cleavable linkers. Using trastuzumab conjugated with a payload linker consisting of this platform and exo-EVC-Exatecan (APL-1082), we examined key parameters, including efficacy and pharmacokinetic profiles in rat models, to directly compare it with the clinically validated trastuzumab-deruxtecan (T-DXd, Enhertu).
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