PETIT, Robert,PERRY, Kyle,PRINCIOTTA, Michael F.,OCONNOR, Daniel J.,CODER, Brandon,BALLI, David
申请号:
USUS2017/064016
公开号:
WO2018/102585A1
申请日:
2017.11.30
申请国别(地区):
WO
年份:
2018
代理人:
摘要:
Provided herein are systems comprising recurrent cancer mutation immunotherapy compositions and personalized neoepitope immunotherapy compositions. Also provided are recurrent cancer mutation immunotherapy compositions comprising a recombinant Listeria strain comprising a nucleic acid comprising a nucleic acid comprising an open reading frame encoding a recombinant fusion polypeptide comprising one or more antigenic peptides (e.g., fused to a PEST-containing peptide) from cancer-associated proteins. The antigenic peptides can comprise one or more or all of an antigenic peptide comprising a recurrent cancer mutation, an antigenic peptide comprising a heteroclitic mutation, or an antigenic peptide fused to a ubiquitin protein. Also provided are recurrent cancer mutation immunotherapy compositions comprising a recombinant Listeria strain comprising a nucleic acid comprising an open reading frame encoding a fusion polypeptide, wherein the fusion polypeptide comprises a PEST-containing peptide fused to two or more antigenic peptides, wherein each of the antigenic peptides comprises a recurrent cancer mutation, and wherein at least two of the antigenic peptides comprise different recurrent cancer mutations and are fragments of the same cancer-associated protein. Also provided are personalized immunotherapy compositions comprising a recombinant Listeria strain comprising a nucleic acid comprising an open reading frame encoding a fusion polypeptide, wherein the fusion polypeptide comprises a PEST-containing peptide fused to one or more antigenic peptides, wherein each of the antigenic peptides comprises a cancer-specific neoepitope comprising a cancer-specific mutation found in a cancer sample from a subject but not in a healthy biological sample from the subject. Also provided are recombinant fusion polypeptides, nucleic acids encoding fusion polypeptides, and methods of generating such compositions. Also provided are methods of inducing an anti-tumor-associated-antigen im