News Article

Caliviri Demonstrates That RNA Processing Errors Are a Rich Source of Tumor Neoantigens for Cancer Vaccines
Date: Oct 03, 2019
Source: Business Wire ( click here to go to the source)

Featured firm in this article: Calviri Inc of Tempe, AZ

TEMPE, Ariz.--(BUSINESS WIRE)--Calviri, Inc., a biotech startup spun out of Arizona State University Biodesign Institute, focused on prevention and treatment of cancer, announced results that demonstrate the potential of a prophylactic vaccine against cancer. The study of RNA processing errors in tumors highlighted that a large number of frameshift neoantigens are produced. This new class of neoantigens are shown to be effective as components in a vaccine against cancer.

Published in Nature Scientific Reports, scientists at Calviri, Inc. and the Center for Innovations in Medicine at Arizona State University reported examining RNA in tumors as a source of neoantigens -- specifically frameshift neoantigens generated from processing errors at the RNA level. They show in breast cancer that there are frequent intron splicing errors that, if translated, would create frameshift peptides. Mouse tumor models for melanoma and breast cancer revealed these frameshift neoantigens conferred partial protection as vaccines. Adding more neoantigen peptides to the vaccine increased protection. This demonstrates that the frameshift neaoantigens can be effectively pooled and indicates the potential for achieving further improved efficacy as additional neoantigens are evaluated.

In tumor cells both RNA transcription through microsatellites and RNA splicing can result in up to 220,000 different frameshift neoantigens. Calviri developed a simple approach to screen through these neoantigens. An array of peptides corresponding to all of these possible frameshift neoantigens is used to test patient blood for antibodies produced by their tumors against them. "We are very encouraged by finding a significant amount of recurrent immune activity against frameshift neoantigens. Without any need for tumor biopsies and antigen discovery, this cache of shared, immunogenic neoantigens makes designing generalized cancer vaccines feasible. The simplicity and affordability of these new vaccines should enable their access to people worldwide. In our continued studies, we will determine the efficacy of our shared, RNA-error derived neoantigen vaccines compared to personal vaccines," stated Stephen Albert Johnston, CEO of Calviri, Inc.

Since there are a limited number (~220,000) of frameshift peptides that any tumor could make through errors in RNA transcription or splicing, the authors were able to create peptide arrays that displayed all of them. This would not be feasible with mutations that could occur in DNA since there are too many possibilities. Blood samples from patients with five different types of cancer (lung, breast, glioblastoma, gastric and pancreatic) were screened on the arrays to determine which frameshift peptides were recognized by blood-antibodies. They discovered approximately 20% of the arrayed peptides were commonly bound by antibodies present in patients with the same cancer type, and a small percent of peptides were commonly bound by antibodies from all patients. This finding suggests that pre-made vaccines could be developed for each type of cancer. The team suggests that a general prophylactic vaccine may also be possible from the shared, "public" neoantigens.