To accomplish this, they had to thread a needle in immune function, shrinking tumors without triggering unwanted autoimmune responses.
The new research, performed in animals, is not ready for clinical use in humans. However, the approach, making use of a key protein to control immune function, lends itself to further study using candidate drugs that employ the same mechanisms.
Study leader Wayne W. Hancock, M.D., Ph.D., of the Division of Transplant Immunology at The Children's Hospital of Philadelphia (CHOP) said that this preclinical study demonstrates proof of principle that using a drug to regulate the function of a special, immunosuppressive subset of so-called T-regulatory (Treg) cells safely controls tumour growth.
He asserted that it really moves the field along towards a potentially major, new cancer immunotherapy.
Hancock asserted that there is a basic paradox in immunology: why doesn't the immune system prevent cancer in the first place?
He explained that the answer is complicated but much of it involves a delicate balancing act among elements of the immune system: while immunity protects us against disease, an overly aggressive immune response may trigger dangerous, even life-threatening, autoimmune reactions in which the body attacks itself.
In the current study, Hancock focused on a subtype of immune cells called Foxp3+ Tregs, for short. Tregs were already known to limit autoimmunity, but often at the cost of curtailing immune responses against tumors.
He said that the team needed to find a way to reduce Treg function in a way that permits antitumor activity without allowing autoimmune reactions.
His group showed that inhibiting the enzyme p300 can affect the functions of another protein, Foxp3, which plays a key role in controlling the biology of Tregs. By deleting the gene that expresses p300, the researchers safely reduced Treg function and limited tumor growth in mice. Notably, they also achieved the same effects on p300 and Tregs in mice by using a drug that inhibits p300 in normal mice.
The study has been published in Nature Medicine.
--ANI (Posted on 19-08-2013)