Viral Neoepitopes and Uses Thereof
Contemplated antiviral/cancer treatments comprise analysis of neoepitopes from viral DNA that has integrated into the host genome, and design of immunotherapeutic agents against such neoepitopes.
1 . A computer-based viral neoepitope analysis engine system, comprising:
at least one reference database storing reference nucleic acid sequences including at least one viral associated nucleic acid sequence;
at least one non-transitory computer readable memory store software instructions; and
at least one processor coupled with the at least one reference database and the at least one memory, and that executes the following operations upon execution of the software instructions:
obtaining omics data from a biopsy of a patient;
identifying at least one antigen having a length of 5 to 30 amino acids and that is encoded in nucleic acid sequences of the omics data by comparing the omics data from the patient biopsy with the at least one viral associated nucleic acid sequence in the at least one reference database;
identifying at least one of the at least one antigen as an HLA-matched antigen that is matched with respect to an HLA type of the patient and has a binding affinity equal to or less than 100 nM with an HLA-type of the patient, where the HLA type of the patient comprises a predicted HLA type from a composite de Bruijn graph generated from the omics data from the patient biopsy; and
enabling production or preparing of an immunotherapeutic composition comprising a recombinant virus that includes the nucleic acids sequence of the HLA-matched antigen or a recombinant cell expressing a recombinant protein that targets the HLA-matched antigen.
2 . The system of claim 1 , wherein the viral associated nucleic acid sequence comprises a sequence from a viral associated tumor.
3 . The system of claim 1 , wherein the viral associated nucleic acid sequence comprises a Human Papilloma Virus (HPV) nucleic acid sequence.
4 . The system of claim 1 , wherein viral associated nucleic acid sequence comprises a chimeric reference nucleic acid sequence.
5 . The system of claim 4 , wherein the chimeric reference nucleic acid sequence comprise at least one viral nucleic acid sequence and a mammalian nucleic acid sequence.
6 . The system of claim 1 , wherein the de Bruijn graph comprises a colored de Bruijn graph.
7 . The system of claim 6 , wherein the predicted HLA type is selected based on votes using k-mers that match a corresponding segment in known HLA alleles.
8 . The system of claim 7 , wherein the de Bruijn graph comprises k-mer edges from the omics data.
9 . The system of claim 8 , wherein the k-mers having length of 3 to 300 bases.
10 . The system of claim 1 , wherein the patient biopsy is a tumor biopsy from the patient.
11 . The system of claim 10 , Wherein the tumor biopsy is a cervical carcinoma from the patient.
12 . The system of claim 1 , wherein the patient biopsy is a pre-neoplastic lesion biopsy from the patient.
13 . The system of claim 1 , wherein the patient biopsy is a lymph node biopsy proximal to a tumor of the patient.
14 . The system of claim 1 , wherein the nucleic acid encoding the HLA-matched antigen further includes a segment encoding a trafficking signal to direct expression of the HLA-matched antigen to MHC-I and/or MHC-II presentation pathways.
15 . The system of claim 1 , wherein the nucleic acid encoding the HLA-matched antigen has a concatemeric arrangement comprising a segment encoding multiple HLA-matched antigens.
16 . The system of claim 1 , wherein the recombinant virus is an adenovirus with deleted E2b gene function.
17 . The system of claim 1 , wherein the omics data comprises whole genome data.
18 . The system of claim 1 , wherein the omics data comprises whole transcriptome data.
19 . The system of claim 1 , wherein the HLA-matched antigen is a neoepitope that binds to or activates T-cells.
20 . The system of claim 19 , wherein the T-cells comprise CD4+o r CD8+ T-cells.