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.

PubMed

Insights

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.

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