NEOANTIGENS AND USES THEREOF
Disclosed herein relates to immunotherapeutic compositions comprising immunotherapeutic peptides comprising neoepitopes, polynucleotides encoding the immunotherapeutic peptides, antigen presenting cells comprising the immunotherapeutic peptides or polynucleotides, or T cell receptors specific for the neoepitopes. Also disclosed herein is use of the immunotherapeutic compositions.
1 . A method of treating cancer in a subject in need thereof, the method comprising:
(a) administering to the subject a first pharmaceutical composition comprising autologous T cells, wherein the autologous T cells comprise:
(i) a first plurality of autologous T cells stimulated with antigen presenting cells (APCs) that present a first neoepitope as a complex with a class II HLA protein, wherein the class II HLA protein is a protein encoded by a class II HLA allele of the subject; or,
(ii) a second plurality of autologous T cells stimulated with APCs that present a second neoepitope as a complex with a class I HLA protein, wherein the class I HLA protein is a protein encoded by a class I HLA allele of the subject; wherein the first neoepitope and the second neoepitope are from a first protein, and
wherein the first neoepitope and the second neoepitope comprise the same mutation;
(b) subsequent to (a), administering to the subject a second pharmaceutical composition comprising one or more polypeptides comprising a neoepitope, or one or more polynucleic acids encoding the one or more polypeptides.
2 . The method of claim 1 , wherein the one or more polypeptides comprising a neoepitope comprises the first neoepitope and the second neoepitope.
3 . The method of claim 1 , wherein the first neoepitope is from 9 to 25 amino acids in length and the second neoepitope is from 8 to 13 amino acids in length.
4 . The method of claim 1 , wherein the second plurality of autologous T cells comprises CD8+ T cells; and wherein the first plurality of autologous T cells comprises CD4+ T cells.
5 . The method of claim 4 , wherein the CD8+ T cells or the CD4+ T cells are effector memory T cells.
6 . The method of claim 1 , wherein the APCs of (i) and (ii) are autologous APCs.
7 . The method of claim 1 , wherein the autologous T cells further comprise:
(iii) at least a third plurality of autologous T cells stimulated with antigen presenting cells (APCs) that present a third neoepitope, or
(iv) at least a fourth plurality of autologous T cells stimulated with antigen presenting cells (APCs) that present a fourth neoepitope, wherein the third neoepitope and the fourth neoepitope are from a second protein and comprise the same mutation.
8 . The method of claim 7 , wherein the second pharmaceutical composition comprises one or more polypeptides comprising the third neoepitope and the fourth neoepitope; or one or more polynucleic acids encoding the one or more polypeptides.
9 . The method of claim 7 , wherein the mutation in the third neoepitope and the fourth neoepitope is distinct from the mutation in the first neoepitope and the second neoepitope.
10 . The method of claim 7 , wherein the one or more polypeptides further comprise a third neoepitope and a fourth neoepitope.
11 . The method of claim 7 , wherein the third plurality of autologous T cells are stimulated with antigen presenting cells (APCs) that present the third neoepitope as a complex with a class II HLA protein, wherein the class II HLA protein is a protein encoded by a class II HLA allele of the subject.
12 . The method of claim 7 , wherein the fourth plurality of autologous T cells are stimulated with APCs that present the fourth neoepitope as a complex with a class I HLA protein, wherein the class I HLA protein is a protein encoded by a class I HLA allele of the subject.
13 . The method of claim 1 , wherein the polynucleic acid encoding the encoding the one or more polypeptides is RNA.
14 . The method of claim 1 , wherein the polynucleic acid encoding the one or more polypeptides is DNA.
15 . The method of claim 14 , wherein the polynucleic acid is a vector.
16 . The method of claim 14 , wherein the polynucleic acid is a viral vector.
17 . The method of claim 16 , wherein the viral vector is a retroviral vector, an adenoviral vector or an adeno-associated virus vector.
18 . The method of claim 16 , wherein the viral vector is a lentiviral vector.
19 . The method of claim 15 , wherein the vector comprises a promoter.
20 . The method of claim 1 , wherein (b) is administered at least 21 days after (a).
21 . The method of claim 1 , wherein (b) is administered more than once.
22 . The method of claim 21 , wherein (b) is administered at a time interval of at least two weeks, at least three weeks, at least 1 month, or at least 6 months.
23 . The method of claim 22 , wherein the subject is administered a first dose of (b) following (a), followed by a second or a subsequent dose of (b) at the time interval, wherein the first does of (b) is higher than the second or the subsequent dose of (b).