AI Article Synopsis
- A study investigated how genetic variations in immune-related genes influence the ability of peripheral blood mononuclear cells (PBMC) to kill breast cancer cells when treated with trastuzumab.
- Researchers analyzed PBMCs from 148 healthy donors and 13 breast cancer patients, finding that trastuzumab-treated PBMCs had significantly higher cytotoxicity compared to untreated groups.
- The study identified that individuals with the rs16859030 T genotype had greater trastuzumab-mediated cytotoxicity than those with the CC genotype, indicating that this polymorphism plays a role in treatment effectiveness.
Article Abstract
To investigate the associations between genetic polymorphisms in immunorelated genes and PBMC-induced cytotoxicity to breast cancer cell with the treatment of trastuzumab . Trastuzumab-mediated cytotoxicity of peripheral blood mononuclear cells (PBMC) from 148 healthy donors and 13 BC patients was analyzed by flow cytometry. 16 SNPs in 7 immunorelated genes were genotyped by Sequenom Mass Array Genotype Platform. Cytotoxicity in the trastuzumab treated PBMCs were significantly higher than those of the basal group. A wide variability in trastuzumab-mediated cytotoxicity was observed, and PBMC from individuals with the rs16859030 T genotype generated increased cytotoxicity than those with the CC genotype. The rs16859030 polymorphism affects trastuzumab-mediated cytotoxicity .
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492633 | PMC |
| http://dx.doi.org/10.1080/14622416.2024.2404819 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Trastuzumab-Mediated Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) Enhances Natural Killer Cell Cytotoxicity in HER2-Overexpressing Ovarian Cancer.
Int J Mol Sci
October 2024
Division of Hematology-Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 13496, Republic of Korea.
Ovarian cancer is the deadliest gynecologic cancer. Although human epidermal growth factor receptor-2 (HER2) overexpression, a poor prognostic molecular marker in ovarian cancer, is found in almost 30% of ovarian cancer cases, there are no established therapies for HER2-overexpressing ovarian cancer. In this study, we investigated the efficacy of combined samfenet, a biosimilar compound of trastuzumab, and natural killer (NK) cells in preclinical model of HER2-overexpressing ovarian cancer.
View Article and Find Full Text PDFEffects of immunorelated gene polymorphisms on trastuzumab targeting breast cancer cell .
Pharmacogenomics
October 2024
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Article Synopsis
- A study investigated how genetic variations in immune-related genes influence the ability of peripheral blood mononuclear cells (PBMC) to kill breast cancer cells when treated with trastuzumab.
- Researchers analyzed PBMCs from 148 healthy donors and 13 breast cancer patients, finding that trastuzumab-treated PBMCs had significantly higher cytotoxicity compared to untreated groups.
- The study identified that individuals with the rs16859030 T genotype had greater trastuzumab-mediated cytotoxicity than those with the CC genotype, indicating that this polymorphism plays a role in treatment effectiveness.
Pyrotinib and trastuzumab combination treatment synergistically overcomes HER2 dependency in HER2-positive breast cancer: insights from the PHILA trial.
EBioMedicine
November 2024
Department of Medical Oncology, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; State Key Laboratory of Molecular Oncology, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address:
Article Synopsis
- The PHILA study demonstrates that the combination of pyrotinib, trastuzumab, and docetaxel significantly enhances progression-free survival in untreated HER2-positive metastatic breast cancer patients compared to other treatment options.
- Research conducted included in vitro and in vivo experiments, revealing that the combination therapy is more effective in inhibiting cancer cell growth and blocking the HER2 signaling pathway.
- Findings suggest that this treatment strategy is particularly effective for patients with HER2 dependency, highlighting its potential as an optimal option for managing this type of breast cancer.
Define Critical Parameters of Trastuzumab-Mediated ADCC Assays via Assay Optimization Processes, Focusing on the Impact of Cryopreserved Effector Cells on Assay Performance.
Cancers (Basel)
June 2024
Division of Pharmaceutical Quality Research III (OPQR III), Office of Pharmaceutical Quality Research (OPQR), Office of Pharmaceutical Quality (OPQ), Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA), 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
The mechanisms of mAb-induced ADCC have been well established. However, the ADCC bioassays used to quantify mAb-induced ADCC require continued development/refinement to properly assess and compare the potency of newly developed therapeutic mAbs and biosimilars to meet regulatory requirements. We used trastuzumab and a lactate dehydrogenase (LDH)-based ADCC bioassay as a model to define critical parameters of the ADCC bioassay, describing how several bioassay parameters, including preparation of effector cells, E/T ratio, target cell selection, bioassay media components, and treatment time can influence the data quality of the ADCC activity.
View Article and Find Full Text PDFUniversal CAR T cells targeted to HER2 with a biotin-trastuzumab soluble linker penetrate spheroids and large tumor xenografts that are inherently resistant to trastuzumab mediated ADCC.
Front Immunol
April 2024
Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
CAR T cell therapies face challenges in combating solid tumors due to their single-target approach, which becomes ineffective if the targeted antigen is absent or lost. Universal CAR T cells (UniCAR Ts) provide a promising solution by utilizing molecular tags (linkers), such as biotin conjugated to monoclonal antibodies, enabling them to target a variety of tumor antigens. Recently, we showed that conventional CAR T cells could penetrate the extracellular matrix (ECM) of ADCC-resistant tumors, which forms a barrier to therapeutic antibodies.
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!