Treatment using cytokine encoding RNA
The present disclosure relates to methods and compositions for inducing an immune response in a subject comprising co-administering to the subject RNA encoding peptides or proteins used for vaccination and RNA encoding IL-2 attached to a pharmacokinetic modifying group and/or RNA encoding IL-7 attached to a pharmacokinetic modifying group. The vaccine is particularly effective if an immune checkpoint inhibitor such as an anti-PD-L1 antibody is further administered. The present disclosure further relates to methods involving the target-specific delivery of a cytokine to a target organ or target tissue.
1 . A method for inducing an immune response against an antigen in a subject comprising administering to the subject:
a. RNA encoding IL-2 attached to a moiety selected from the group consisting of serum albumin, an immunoglobulin Fc domain, transferrin, and Fn3 (extended pharmacokinetic (PK) IL-2) and RNA encoding extended IL-7 attached to a moiety selected from the group consisting of serum albumin, an immunoglobulin Fc domain, transferrin, and Fn3 (extended pharmacokinetic (PK) IL-7); and
b. RNA encoding a peptide or protein comprising an epitope for inducing said immune response against said antigen in said subject.
2 . A medical preparation comprising:
a. RNA encoding IL-2 attached to a moiety selected from the group consisting of serum albumin, an immunoglobulin Fc domain, transferrin, and Fn3 (extended-pharmacokinetic (PK) IL-2) and RNA encoding IL-7 attached to a moiety selected from the group consisting of serum albumin, an immunoglobulin Fc domain, transferrin, and Fn3 (extended-pharmacokinetic (PK) IL-7); and
b. RNA encoding a peptide or protein comprising an epitope for inducing an immune response against an antigen in a subject.
3 . The medical preparation of claim 2 , wherein the moiety of the extended-PK IL-2 is mouse serum albumin or human serum albumin.
4 . The medical preparation of claim 2 , further comprising:
c. an immune checkpoint inhibitor targeting the interaction between PD-1 and PD-L1.
5 . The medical preparation of claim 4 , wherein the immune checkpoint inhibitor is an antibody or antibody fragment that targets PD-1, PD-L1, or CTLA-4.
6 . The medical preparation of claim 2 , which is a pharmaceutical composition comprising the RNAs.
7 . The medical preparation of claim 6 , wherein the pharmaceutical composition further comprises one or more pharmaceutically acceptable carriers, diluents and/or excipients.
8 . The medical preparation of claim 2 , wherein the RNA encoding extended-PK IL-2, or the RNA encoding extended-PK IL-7, or both the RNA encoding extended-PK IL-2 and the RNA encoding extended-PK IL-7 is present in a form selected from a liquid form, a solid form, or a combination thereof.
9 . The medical preparation of claim 8 , wherein the solid form is a frozen form or a dehydrated form.
10 . The medical preparation of claim 9 , wherein the dehydrated form is a freeze-dried or spray-dried form.
11 . The medical preparation of claim 2 , wherein each respective moiety is mouse serum albumin or human serum albumin.
12 . The medical preparation of claim 2 , wherein the IL-2 of the extended-PK IL-2 is human IL-2.
13 . The medical preparation of claim 2 , wherein the IL-7 of the extended-PK IL-7 is human IL-7.
14 . The medical preparation of claim 2 , wherein the IL-2 of the extended-PK IL-2 is human IL-2 and the IL-7 of the extended-PK IL-7 is human IL-7.
15 . The medical preparation of claim 14 , wherein the moiety of the extended-PK IL-2 is serum albumin and the moiety of the extended-PK IL-7 is serum albumin.
16 . The medical preparation of claim 2 , wherein the IL-2 of the extended-PK IL-2 comprises the amino acid sequence of SEQ ID NO: 1.
17 . The medical preparation of claim 16 , wherein the moiety of the extended-PK IL-2 comprises the amino acid sequence set forth in SEQ ID NO: 5.
18 . The medical preparation of claim 2 , wherein the IL-7 of the extended-PK IL-7 comprises the amino acid sequence of SEQ ID NO: 2.
19 . The medical preparation of claim 18 , wherein the moiety of the extended-PK IL-7 comprises the amino acid sequence set forth in SEQ ID NO: 5.
20 . The medical preparation of claim 2 , wherein the IL-2 of the extended-PK IL-2 comprises the amino acid sequence of SEQ ID NO: 1 and the IL-7 of the extended-PK IL-7 comprises the amino acid sequence of SEQ ID NO: 2.
21 . The medical preparation of claim 20 , wherein the moiety of the extended-PK IL-2 comprises the amino acid sequence set forth in SEQ ID NO: 5 and the moiety of the extended-PK IL-7 comprises the amino acid sequence set forth in SEQ ID NO: 5.
22 . The method of claim 1 , wherein the moiety of the extended-PK IL-2 is mouse serum albumin or human serum albumin.
23 . The method of claim 1 , further comprising administering to the subject:
c. an immune checkpoint inhibitor targeting the interaction between PD-1 and PD-L1.
24 . The method of claim 23 , wherein the immune checkpoint inhibitor is an antibody or antibody fragment that targets PD-1, PD-L1, or CTLA-4.
25 . The method of claim 1 , wherein each respective moiety is mouse serum albumin or human serum albumin.
26 . The method of claim 1 , wherein the IL-2 of the extended-PK IL-2 is human IL-2.
27 . The method of claim 1 , wherein the IL-7 of the extended-PK IL-7 is human IL-7.
28 . The method of claim 1 , wherein the IL-2 of the extended-PK IL-2 is human IL-2 and the IL-7 of the extended-PK IL-7 is human IL-7.
29 . The method of claim 28 , wherein the moiety of the extended-PK IL-2 is serum albumin and the moiety of the extended-PK IL-7 is serum albumin.
30 . The method of claim 1 , wherein the IL-2 of the extended-PK IL-2 comprises the amino acid sequence of SEQ ID NO: 1.
31 . The method of claim 30 , wherein the moiety of the extended-PK IL-2 comprises the amino acid sequence set forth in SEQ ID NO: 5.
32 . The method of claim 1 , wherein the IL-7 of the extended-PK IL-7 comprises the amino acid sequence of SEQ ID NO: 2.
33 . The method of claim 32 , wherein the moiety of the extended-PK IL-7 comprises the amino acid sequence set forth in SEQ ID NO: 5.
34 . The method of claim 1 , wherein the IL-2 of the extended-PK IL-2 comprises the amino acid sequence of SEQ ID NO: 1 and the IL-7 of the extended-PK IL-7 comprises the amino acid sequence of SEQ ID NO: 2.
35 . The method of claim 34 , wherein the moiety of the extended-PK IL-2 comprises the amino acid sequence set forth in SEQ ID NO: 5 and the moiety of the extended-PK IL-7 comprises the amino acid sequence set forth in SEQ ID NO: 5.