Intracellular Cancer-Specific Proteins Remain Inaccessible to Current Technologies05 Feb 2018 • by Natalie Aster
LONDON – There are appr. 3-4 times more intracellular targets compared to surface protein targets. It is suggested that close to 75% of secreted or intracellular cancer targets are not accessible for conventional mAb and CAR T-cell therapies. In such as way, scores of intracellular target proteins, comprising overexpressed oncogene proteins, mutated tumour suppressor genes and translocated gene products, are still untapped by now. A chunk of the intracellular antigen-related proteins is relegated to protein fragments that are ultimately available on the outer layer of cells as a composite antigen made up of a variable linear sequence peptide hidden within a MHC molecule, also termed as HLA class I, for recognition by TCRs.
Groundbreaking technologies addressing intracellular cancer targets presented as peptide-MHC epitopes on the cell surface encompass TCR-engineered T-cells and recombinant TCR fusion proteins, alongside TCR-like (TCRL) or TCR mimic (TCRm) antibodies. Cell-penetrating biological agents are directly aiming at targets in the cell and the nucleus, homing in on mainly PPIs.
To date, only 1 recombinant TCR fusion protein and 1 cell-penetrating peptide (CPP) have progressed to clinical investigation mirroring the elevated degree of technology related rough waters. Nevertheless, in 2015, the leader in the recombinant TCR fusion proteins domain completed Europe’s largest ever financing round by a privately held life sciences firm, raising USD 320 million, attesting to that a large reward is awaiting those who create and validate technologies to untap the intracellular target pool.
Thus, new technologies are required to address traditionally undruggable targets and sophisticated mechanisms, like intracellular protein-protein interactions like Ras or p53, beta-catenin and Myc.
More granular and comprehensive market information can be found in the report “Intracellular Targets made druggable by TCR-like Antibodies, TCR Fusion Proteins & Cell-Penetrating Biologics 2018” drawn up by La Merie Publishing.