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CARTAR: a comprehensive web tool for identifying potential targets in chimeric antigen receptor therapies using TCGA
Miguel Hernandez-Gamarra1,2, Alba Salgado-Roo1,2, Eduardo Dominguez2
1Genomic Medicine Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela, Av. Barcelona, 15706 A Coruña, Spain.
Briefings in Bioinformatics
|July 8, 2024
Summary
This study introduces CARTAR, a novel website for identifying optimal targets for chimeric antigen receptor (CAR) therapy. CARTAR aids in selecting tumor-associated antigens for effective and safe cancer treatment.
Area of Science:
- Immunology
- Oncology
- Bioinformatics
Background:
- Chimeric antigen receptor (CAR) therapy represents a significant advancement in cancer treatment, utilizing engineered immune cells to target cancer.
- The selection of appropriate CAR targets is critical for therapeutic efficacy, safety, and specificity, necessitating careful analysis of tumor-associated antigens.
- Existing methods for CAR target identification can be labor-intensive and may not fully leverage comprehensive genomic and transcriptomic datasets.
Purpose of the Study:
- To develop and present CARTAR, a comprehensive web-based platform for the systematic identification and analysis of potential CAR therapy targets.
- To provide researchers with tools to pinpoint tumor-associated antigens with high selectivity and assess potential off-tumor toxicities.
- To facilitate the rational design of CAR therapies, including dual CARs, by enabling exploration of target expression in both patient tumors and cell lines.
Main Methods:
- Leveraged large-scale expression data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression Project (GTEx).
- Integrated data from the Cancer Cell Line Encyclopedia (CCLE) to assess candidate target expression in relevant cell line models.
- Developed a user-friendly website (CARTAR) to host these analytical tools for public access.
Main Results:
- The CARTAR platform enables the identification of potential CAR targets by analyzing tumor-specific antigen expression.
- Tools within CARTAR facilitate the assessment of target selectivity and specificity, crucial for minimizing on-target, off-tumor toxicities.
- The website allows for the exploration of candidate target expression across diverse cancer types and cell lines, supporting informed therapeutic design.
Conclusions:
- CARTAR is the first dedicated website for the systematic search of suitable CAR therapy targets, significantly advancing the field of personalized cancer immunotherapy.
- The platform empowers researchers to rationally design more effective and safer CAR therapies by providing comprehensive target identification and validation tools.
- The accessibility of CARTAR is expected to accelerate the development and clinical translation of novel CAR-based cancer treatments.
