Avoiding immune destruction
Aberrant hyperexpression of the RNA binding protein FMRP in tumors mediates immune evasion
Upregulation of the neuronal fragile X mental retardation protein in cancer cells suppresses proinflammatory signals to circumvent tumor immunityJournal Science, Hanahan et al, November 2022
A significant fraction of human tumors express moderate to high levels of FMRP
OPNA is developing small
molecule inhibitors of FMRP
The escape of cancer cells from immune attack remains a main obstacle to cancer treatment today. Initially identified as a key RNA-binding protein in the brain, fragile-X mental retardation protein (FMRP) has recently been shown to play a key role in tumor immune escape.
Mechanistically, FMRP directly regulates multiple immuno-regulatory factors to suppress T cells from attacking cancer cells; the high levels of FMRP across most types of solid tumors prevent immune attack, while FMRP-deficient tumors become massively infiltrated with T cells that impair tumor growth and prolong survival.
Opna Bio is developing first-in-class small molecule drugs against this novel target, FMRP, with the goal of converting immunologically “cold” tumors with poor T cell infiltration to “hot” tumors that are unlocked to T cell-mediated immune attack.