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 method of treating a patient having a Human Papilloma Virus (HPV) viral infection, the method comprising:
obtaining a tissue sample from the patient and analyzing the tissue sample to obtain omics data;
comparing the omics data of the patient's tissue sample with omics data of a reference HPV viral genome to determine a plurality of nucleic acid sequences in the patient tissue sample encoding antigens for the HPV virus, wherein each of the antigens has a length of between 5 and 30 amino acids;
identifying an HLA-matched antigen from the plurality of nucleic acid sequences encoding antigens for the HPV virus, wherein the HLA-matched antigen is matched with respect to an HLA type of the patient and has a dissociation constant equal to or less than 100 nM with an HLA-type of the patient; and
treating the patient by administering to the patient having the HPV viral infection an effective amount of an immunotherapeutic composition comprising a recombinant virus that includes the nucleic acid encoding the HLA-matched antigen or a recombinant cell expressing a recombinant protein that targets the HLA-matched antigen, wherein the administration triggers an immune response against the HLA-matched antigen.
2. The method of claim 1 wherein the plurality of nucleic acid sequences encoding the antigens for the virus are obtained from a sample of the patient.
3. The method of claim 1 wherein the sample of the patient is a cancerous sample.
4. The method of claim 1 wherein the HLA-type of the patient is determined from omics data of the patient.
5. The method of claim 1 wherein the dissociation constant of the HLA-matched antigen is determined in silico.
6. The method of claim 1 wherein the nucleic acid encoding the HLA-matched antigen further includes a segment encoding a trafficking signal and thereby directs expression of the HLA-matched antigen to MHC-I and/or MHC-II presentation pathways.
7. A method of making a patient-specific immunotherapeutic composition for treating a patient having a Human Papilloma Virus (HPV) viral infection, comprising:
obtaining a tissue sample from the patient and analyzing the tissue sample to obtain omics data;
comparing the omics data of the patient's tissue sample with omics data of a reference HPV viral genome to determine a plurality of nucleic acid sequences in the patient tissue sample encoding antigens for the HPV virus, wherein each of the antigens has a length of between 5 and 30 amino acids;
identifying an HLA-matched antigen from the plurality of nucleic acid sequences encoding antigens for the HPV virus, wherein the HLA-matched antigen is matched with respect to an HLA type of the patient and has a dissociation constant equal to or less than 100 nM with the HLA-type of the patient; and
generating an immunotherapeutic composition comprising a recombinant virus that includes the nucleic acid encoding the HLA-matched antigen or a recombinant cell expressing a recombinant protein that targets the HLA-matched antigen.
8. The method of claim 7 wherein the HLA-type of the patient is determined from omics data of the patient.
9. The method of claim 7 wherein the virus is a tumor-associated virus.
10. The method of claim 7 wherein the dissociation constant of the HLA-matched antigen is determined in silico.
11. The method of claim 7 wherein the recombinant virus is an adenovirus with deleted E2b gene function.
12. The method of claim 7 wherein the nucleic acid encoding the HLA-matched antigen has a concatemeric arrangement comprising a segment encoding multiple HLA-matched antigens.
13. The method of claim 7 wherein the nucleic acid encoding the HLA-matched antigen further includes a segment encoding a trafficking signal and thereby directs expression of the HLA-matched antigen to MHC-I and/or MHC-II presentation pathways.
14. A method of using omics data from a patient having a Human Papilloma Virus (HPV) viral infection, comprising:
comparing the omics data of the patient with omics data of a reference HPV viral genome to identify in the patient omics data a plurality of nucleic acid sequences encoding antigens for the HPV virus, wherein each of the antigens has a length of between 5 and 30 amino acids;
identifying an HLA-matched antigen from the plurality of HPV viral antigens, wherein the HLA-matched antigen is matched with respect to an HLA type of the patient and has a dissociation constant equal to or less than 100 nM with the HLA-type of the patient; and
making a nucleic acid construct encoding the HLA-matched antigen, wherein the nucleic acid construct includes a promotor operably coupled to a sequence portion that encodes the HLA-matched antigen.
15. The method of claim 14 wherein the omics data are whole genome data and/or whole transcriptome data.
16. The method of claim 14 wherein the HLA-type of the patient is determined from the omics data of the patient.
17. The method of claim 14 wherein the nucleic acid construct further includes a segment encoding a trafficking signal and thereby directs expression of the HLA-matched antigen to MHC-I and/or MHC-II presentation pathways.