We’ve found Cancer’s Achilles' Heel
We directly detect and measure a person’s immune responses to mistakes made by tumors, with a simple blood test.
This has revealed a powerful and plentiful new source of tumor specific neoantigens, RNA-error derived frameshift peptides.
These immunogenic antigens provide the inroad to unique diagnostics for early detection, and vaccines to treat or prevent cancer from happening in the first place.
In normal cells, DNA information is transcribed to messenger RNA (mRNA) then the information contained in the mRNA molecule is translated into proteins.
The quality control that exists in a normal cell ensures that the protein products are accurate and any proteins with mistakes are either repaired or removed quickly.
In all cells, errors in RNA transcription and processing occur more than 100-fold more frequently than errors in DNA replication.
In tumor cells, RNA error rate is further escalated relative to that in healthy cells, and normal repair systems are compromised and overwhelmed. Consequently, many of these tumor-cell RNA mistakes are translated in incorrect reading frames. This generates frameshifted peptide tails at the C termini of normal protein sequences.
RNA-error-derived-neoantigens (REDNs) are immunogenic
We have shown that these frameshift peptides can be presented to the surface or released by tumor cells and then recognized by the host immune system as neoantigens. Both T and B cells are activated.
Activated plasma B cells proliferate and secrete highly amplified levels of antibodies that specifically recognize the tumor RNA-error derived neoantigens (REDNs).
Antibody responses to REDNs are measured on our microchips
The antibodies in a cancer patient’s blood can be used to determine what REDNs their tumor is making. This can be simply and sensitively done by probing a frameshift-peptide array with a small sample of their blood. For this purpose, we developed a highly competitive microchip carrying the millions of frameshift peptides that RNA processing errors could produce.
The profiles of REDN binding activity associated with cancer patients serve as diagnostics.
The REDNs bound by antibodies in cancer patients’ blood samples serve as components for both therapeutic and preventative vaccines.