Our Science
Central Dogma refers to the transcription of DNA’s information into messenger RNA (mRNA) and then its translation into proteins- the actors in biology.
Very effective DNA proofreading and repair processes have evolved to maintain the integrity of a cell’s genomic DNA.
Though less stringent, there are also quality control systems for its processing into mRNA and protein. Mistakes are more common than in DNA synthesis, but still relatively rare.
Healthy Cell
The accuracy of Central Dogma’s information flow is compromised in tumor cells to support rapid, uncontrolled growth. While DNA integrity is somewhat still maintained, RNA and protein processing run largely unchecked.
Consequently, many aberrant RNAs are generated by tumor cells and translated into protein variants. Many of these protein variants are created by a shift in the ribosome’s coding frame, and result in large changes in the protein sequence. These frameshifted sequences are strongly recognized by the immune system as non-self “neoantigens”.
Tumor Cell
Our Technology
Mistakes made by tumor cells in their Central Dogma processes that are downstream of DNA had been untapped. We discovered that these mistakes are a plentiful, powerful source of tumor-specific neoantigens. We build them as neopeptides on semiconductor chips, then query an individual’s blood-antibodies for immune responses to the arrayed neopeptides. Since antibodies are vastly amplified by the presence of a tumor’s neoantigens, the antibodies serve as very sensitive biomarkers of cancer. The antibodies also direct us to those neoantigens that are made by tumors. These tumor neoantigens become valuable components for therapeutic and preventative vaccination against disease.
Semiconductor Chips
Biology
Calviri's Technology
How It Works
We Build Biology on Microchips to Detect Cancer Activity
We have shown that frameshift peptides generated from errors in tumor cell RNA processing are presented on the tumor’s surface or released by it as neoantigens. These are called RNA-Error Derived Neoantigens (REDNs).
The REDNs are recognized by the host immune system, activating both T and B cells to proliferate.
Each activated plasma B cell secretes highly amplified levels of antibodies that specifically recognize the REDNs.
The Biology:
Identifying Frameshifted Peptides Tails on Protein Sequences
If antibodies to REDNs can be detected and measured in patients, then they could be the basis for developing a new class of cancer diagnostics and vaccines.
We learned to detect and measure REDN-specific antibodies in patient blood samples by building high-density semiconductor chips that display millions of predicted REDN ligands.
We developed a competitive immunoassay that captures these biologically important binding activities.
The antibody binding activities associated with cancer patients, but not healthy individuals, serve as sensitive biomarkers to detect cancer on our Diagnostic chips. The REDN neopeptides bound by antibodies in cancer patients’ blood, but not that of healthy individuals on our Discovery chips, define components for both therapeutic and preventative vaccines.
The Chip:
Identifying Frameshifted Peptides Tails on Protein Sequences
Calviri announced the successful completion of the Vaccine Against Canine Cancer Study (VACCS) on May 4, 2024; a five-year clinical trial investigating a novel preventative cancer vaccine in dogs. This multi-center, double-blind, placebo-controlled study, the largest of its kind in veterinary oncology, represents a significant milestone in the fight against canine cancer.
Publications
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