CA103 is a genetically engineered Adenovirus serotype 5/3 carrying a bispecific short hairpin RNA (shRNA) targeting the Androgen Receptor (AR) and mTOR in advanced castration resistant prostate cancer (CRPC). The AR pathway in CRPC is crucial, since conventional hormonal therapy with LHRH antagonists or agonists in this patient population is less effective. Resistance to these therapies makes it possible for cancer cells to reactivate the AR pathway for their survival and growth.
It is also known that the activation of the androgen receptor in prostate cancer leads to high activity of the mTOR pathway and therefore we designed CA103 to be able to knock down both the AR and mTOR signal transductions.
For CA103 to bind with high affinity to cancer cells we modified it so that it has a special knob capable to bind to the desmoglein 2 (DSG2) receptor, which is highly expressed on various types of cancer cells.
CA103 replicates in cancer cells only because of its human telomerase reverse transcriptase promotor (hTERT) that is activated by cancer specific transcription factors. Some of our potential targets for CA103 are breast and prostate cancers