Synthetic Thymus Hormone Increases Therapeutic Power of Brain Cancer Drugs

A synthetic hormone, based on one produced by the thymus gland, has been shown to boost the effects of chemotherapeutic agents used to treat glioblastoma, an aggressive and deadly form of brain cancer.

Investigators at Brown University (Providence, RI, USA) worked with a synthetic form of thymosin alpha 1 (Talpha1 or thymalfasin), which is an analogue of the hormone thymosin produced naturally by the thymus gland. Since thymosin is being used in Europe to treat cancer, the American group decided to evaluate the potential of the synthetic analogue.

Talpha1 is an immunomodulator that increases interleukin-2 (IL-2) production and T-cell proliferation. In the current study, the investigators examined the potential therapeutic effects of Talpha1 in experimental in vivo glioblastoma, and characterized Talpha1's anti-tumor effects in vitro. In addition, Rar 9L cancer cells were implanted into the right frontal lobe of adult Long Evans rats. The rats were then treated with Talpha1 alone or in conjunction with the chemotherapeutic drug BNCU (Carmustine) or with only BNCU.

Results published in the December 2009 issue of the Journal of Oncology revealed that while Talpha1 had no direct effect on viability or mitochondrial function, it increased expression of proapoptosis genes, including FasL, FasR, and TNF-alpha-R1 (65.89%, 44.08%, and 22.18%, respectively), and increased 9L cell sensitivity to oxidative stress. Moreover, Talpha1 enhanced 9L cell sensitivity to both Granzyme B- and BCNU-mediated killing.

"We looked at giving chemo plus Talpha1 as a sort of immune booster," explained senior author Dr. Suzanne de la Monte, professor of neuroscience at Brown University. "What we found is that when you give Talpha1 and the chemo agent together, not only do you have a slower rate of tumor growth with cells being killed, but there have also been cures. We achieved a 25% cure rate in these animal models. Talpha1 sensitizes the tumor cells to the chemotherapeutic agent, giving the agent more of an impact upon the tumor than it would have on its own. The thymic hormone is actually working to boost immune response and basically activates a killing of the tumor cells."

The next step will be to evaluate the drug combination in a Phase I clinical trial. "You are talking about a disease where people are dead within months. There is no cure, said Dr. de la Monte."

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