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We’ve found Cancer’s "Achilles' Heel"

We discovered that tumor cells make many, many mistakes in RNA processing that aren’t made in healthy cells. These mistakes make “foreign” peptides that a person’s immune system will recognize.  Just as the mythological Achilles seemed invulnerable, his enemy discovered his unprotected heel and killed him. We will use tumors’ previously hidden mistakes in RNA and protein processing to end cancer. 

 

We can sensitively detect immune responses to these tumor peptides in a simple blood test.

Our Technology

Mistakes are rarely made in genomic DNA, even with the more relaxed checks and balances of tumor cells. However, mistakes are very common during tumor cells’ synthesis of RNA. We discovered that these mistakes are a plentiful, powerful source of tumor-specific neoantigens- and were untapped. 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 vaccines against disease. 

Semiconductor Chips

Calviri Merges Biology With Semiconductor Technology

Biology

Calviri Merges Biology with Semiconductor Technology

Calviri's Products

It's Biology

Embryonic Stem Cells

Central Dogma refers to the transcription of genomic DNA’s information into messenger RNA (mRNA) and then its translation into proteins- the major 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

Central Dogma of a 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 recognized by the immune system as foreign, non-self “neoantigens”, leading to strong responses. 

Tumor Cell

Central Dogma of a Tumor Cell
Microchip Production
Semiconductor Technology
Diagnostic Cancer Test

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

Antibody amplification event

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 antibodies of healthy individuals on our Discovery chips, define components for both therapeutic and preventative vaccines. 

The Chip:

Identifying Frameshifted Peptides Tails on Protein Sequences

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Science Lab

Technology Application

The First Ever Preventative Canine Cancer Vaccine Trial

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.

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