Send to:

Choose Destination
See comment in PubMed Commons below
Clin Cancer Res. 2009 Sep 15;15(18):5852-60. doi: 10.1158/1078-0432.CCR-08-3163. Epub 2009 Sep 8.

Immunotherapy of metastatic melanoma using genetically engineered GD2-specific T cells.

Author information

  • 1Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.



Genetic engineering of human T lymphocytes to express tumor-directed chimeric antigen receptors (CAR) can produce antitumor effector cells that bypass tumor immune escape mechanisms that are due to abnormalities in protein-antigen processing and presentation. Moreover, these transgenic receptors can be directed to tumor-associated antigens that are not protein-derived, such as the ganglioside GD2, which is expressed in a high proportion of melanoma cells.


We generated chimeric T cells specific for the ganglioside GD2 by joining an extracellular antigen-binding domain derived from the GD2-specific antibody sc14.G2a to cytoplasmic signaling domains derived from the T-cell receptor zeta-chain, with the endodomains of the costimulatory molecules CD28 and OX40. We expressed this CAR in human T cells and assessed the targeting of GD2-positive melanoma tumors in vitro and in a murine xenograft.


Upon coincubation with GD2-expressing melanoma cells, CAR-GD2 T lymphocytes incorporating the CD28 and OX40 endodomains secreted significant levels of cytokines in a pattern comparable with the cytokine response obtained by engagement of the native CD3 receptor. These CAR-T cells had antimelanoma activity in vitro and in our xenograft model, increasing the survival of tumor-bearing animals.


Redirecting human T lymphocytes to the tumor-associated ganglioside GD2 generates effector cells with antimelanoma activity that should be testable in subjects with disease.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk