Cancer vaccine
AssigneePresident and Fellows of Harvard College
InventorsJuan Pablo Maianti, David R. Liu
Life of this patent
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Abstract
Provided herein are systems, compositions, and methods for generating immunogenic peptides or epitopes from tumor associated antigens (e.g., in vivo or ex vivo). Polynucleotides (e.g., genes) encoding the tumor associated antigens may be edited at selected target sites by nucleobase editors comprising a catalytically-inactive Cas9 and a cytosine deaminase, leading to the expression of heteroclitic or cryptic peptides that are more immunogenic than the native peptide derived from the tumor associated antigens. The heteroclitic or cryptic peptide elicit strong tumor-specific immune response (e.g., T-cell response or B-cell response), which inhibits tumor growth and metastasis.
Claims23
A method for producing a heteroclitic epitope in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition comprising:
- (i) a fusion protein comprising (a) a guide nucleotide sequence-programmable DNA-binding protein domain, and (b) a cytosine deaminase domain;
- and
- (ii) a guide nucleotide sequence, wherein the guide nucleotide sequence comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs:
- 724-751, 870-877, 888-905, and 907-985;
- wherein the guide nucleotide sequence of (ii) targets the fusion protein of (i) to a polynucleotide encoding a tumor-specific antigen in a tumor cell;
- and
- wherein the fusion protein changes a target cytosine (C) base to a thymine (T) base via deamination.
Dependencies are inferred from the claim text.