NEW YORK (Reuters Health) - T-cells genetically engineered to target an antigen associated with human breast cancer dramatically extended survival when used as an adjuvant therapy in mice, Australian researchers report.
In fact, mice treated with the engineered T-cells lived significantly longer than those given doxorubicin, 5-fluorouracil or herceptin as adjuvant therapy, Dr. Philip K. Darcy of the Peter MacCallum Cancer Institute in East Melbourne and colleagues report in the August issue of The Journal of Immunology.
The researchers used T-cells with a chimeric receptor designed to react with erbB-2, the same antigen targeted by herceptin. While such T-cells have been used in the past in mouse studies, the Australian team had designed a new version of the receptor with the activation and costimulatory domains located in the same cytoplasmic region.
The researchers injected tumor cells into the mammary tissue of mice, allowing the tumor to grow for 8 days after which it was surgically removed. Significant metastatic disease remained in the animals’ lungs and liver. The mice were then treated with the engineered T-cells, placebo T cells, doxorubicin, 5-fluorouracil or herceptin.
No increased survival was seen in the animals given the drugs, placebo, or surgery only, but survival was significantly increased in mice given the engineered T-cells (p = 0.001), the researchers found.
Among the seven mice given the engineered cells, only two died from metastatic disease; the others were killed by regrowth of the original tumor. “Therefore, T cells were able to inhibit metastases, but were less effective against residual primary tumor regrowth,” the researchers note.
Mice were tested for metastatic disease until day 36. “It will now be of interest, upon accrual of sufficient long-term survivors, to determine the absolute duration of tumor and T cell persistence,” they add.
“Although erbB-2 is expressed on only 25-30% of breast cancers, the approach is potentially more widely applicable due to the availability of singe-chain antibodies against other commonly expressed breast cancer antigens,” the researchers conclude.
“Targeting these other, often coexpressed antigens also renders tumor escape by antigen loss less likely.”
Source: J Immunol 2004;173:2143-2150. [ Google search on this article ]
MeSH Headings:Animal Diseases: Combined Modality Therapy: Disease Models, Animal: Drug Therapy: Recombinant Fusion Proteins: Recombinant Proteins: Therapeutics: Drugs, Investigational: Chemotherapy, Adjuvant: Chimeric Proteins: Analytical, Diagnostic and Therapeutic Techniques and Equipment: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
