79P - Accelerated identification of recurrent neoantigens for the development of off-the-shelf cancer vaccines

Background

Neoantigens, a type of tumor-specific antigens derived from non-synonymous mutations, have become attractive targets for cancer immunotherapy. Approaches targeting private neoantigens derived from mutations that are unique to individual patients’ tumors are costly, labor-intensive and could lead treatment resistance due to antigen loss during clonal evolution. By contrast, vaccines targeting public neoantigens derived from recurrent mutations in cancer driver genes could be designed as “off-the-shelf” vaccines and would be broadly applicable to many cancer patients. However, this therapeutic approach relies on the accurate selection of highly recurrent mutations and identification of immunogenic neoantigens.

Methods

Here, we developed a pipeline with both computational prediction tools and experimental validation assays, known as NEX-NEO to expedite the identification of public neoantigens in 100 patients with colorectal cancer (n=50) and lung cancer (n=50). Furthermore, we developed a robust screening assay using K562 cells expressing HLA-A*11:01 as antigen presenting cells to validate their immunogenicity.

Results

By using NEX-NEO, we constructed an off-the-shelf neoantigen panel of 67 neoantigen candidates which cover 63% and 49% of colorectal and lung cancer patients, respectively. Of the 47 candidates for HLA-A1101 ligand, we identified 23 (48%) immunogenic peptides which are capable of activating CD8 T cells to produce IFN-γ and Granzyme B in PBMC from 10 healthy donors.

Conclusions

In conclusion, our study proposed a novel pipeline for the development of off-the-shelf neoantigen vaccines that could benefit a large proportion of cancer patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Medical Genetics Institute.

Funding

Nexcalibur Therapeutics.

Disclosure

All authors have declared no conflicts of interest.