T-cell recognition of tumor antigens presented on tumor-infiltrating macrophages (TAMs) induces a tumoricidal M1-like phenotype. Resultant indirect immune responses could eliminate not only antigen secreting (Ag), but also antigen negative (Ag) tumor cells via bystander killing. Such broad-spectrum response could eliminate antigenically heterogeneous tumors. Using an model of CD4 T-cell mediated immunity against MHC II negative myeloma cells, bystander killing of Ag cells was ineffective due to strict spatial constraints of Th1-induced TAM cytotoxicity.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292458 | PMC |
| http://dx.doi.org/10.4161/21624011.2014.954953 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
PEGylation of Dipeptide Linker Improves Therapeutic Index and Pharmacokinetics of Antibody-Drug Conjugates.
Bioconjug Chem
January 2025
Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Hydrophobic payloads incorporated into antibody-drug conjugates (ADCs) typically are superior to hydrophilic ones in tumor penetration and "bystander killing" upon release from ADCs. However, they are prone to aggregation and accelerated plasma clearance, which lead to reduced efficacies and increased toxicities of ADC molecules. Shielding the hydrophobicity of payloads by incorporating polyethylene glycol (PEG) elements or sugar groups into the ADC linkers has emerged as a viable alternative to directly adopting hydrophilic payloads.
View Article and Find Full Text PDFTargeting uPAR with an antibody-drug conjugate suppresses tumor growth and reshapes the immune landscape in pancreatic cancer models.
Sci Adv
January 2025
The Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen, Denmark.
Antibody-drug conjugates (ADCs) hold promise to advance targeted therapy of pancreatic ductal adenocarcinoma (PDAC), where the desmoplastic tumor stroma challenges effective treatment. Here, we explored the urokinase plasminogen activator receptor (uPAR) as a candidate ADC target in PDAC, harnessing its massive tumoral and stromal expression in this stroma-dense tumor. We generated a site-specific ADC offering high-affinity, cross-species reactivity, and efficient internalization of the anti-uPAR monoclonal antibody, FL1, carrying a potent anthracycline derivative (PNU-158692).
View Article and Find Full Text PDFThe Golgi complex governs natural killer cell lytic granule positioning to promote directionality in cytotoxicity.
Cell Rep
January 2025
Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Electronic address:
Cytotoxic immune cells mediate precise attacks against diseased cells to maintain organismal health. Their operational unit of killing and host defense is lytic granules (LGs), which are specialized lysosomal-related organelles. Precision in cytotoxicity is achieved by converging the many LGs to the microtubule-organizing center (MTOC) and polarizing these to the diseased cell for secretion.
View Article and Find Full Text PDFOBI-992, a Novel TROP2-Targeted Antibody-Drug Conjugate, Demonstrates Antitumor Activity in Multiple Cancer Models.
Mol Cancer Ther
December 2024
OBI Pharma, Inc., Taipei, Taiwan.
Trophoblast cell surface antigen 2 (TROP2) is highly expressed in multiple cancers relative to normal tissues, supporting its role as a target for cancer therapy. OBI-992 is an antibody-drug conjugate (ADC) derived from a novel TROP2-targeted antibody linked to the topoisomerase 1 (TOP1) inhibitor exatecan via an enzyme-cleavable hydrophilic linker, with a drug-antibody ratio of 4. This study evaluated and compared the antitumor activity of OBI-992 with that of benchmark TROP2-targeted ADCs datopotamab deruxtecan (Dato-DXd) and sacituzumab govitecan (SG) in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models.
View Article and Find Full Text PDFCancer immunotherapy using engineered cytotoxic effector cells has demonstrated significant potential. The limited spatial complexity of existing models, however, poses a challenge to mechanistic studies attempting to approve existing approaches of effector cell-mediated cytotoxicity within a three-dimensional, solid tumor-like environment. To gain additional experimental control, we developed an approach for constructing three-dimensional (3D) culture models using smart polymers that form temperature responsive hydrogels.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!