公开(公告)号：WO2018170313A1

公开(公告)日：2018-09-20

申请号：PCT/US2018/022730

申请日：2018-03-15

Applicant: ADVAXIS, INC. ,  O'CONNOR, Daniel J.

Inventor： O'CONNOR, Daniel J. ,  PETIT, Robert ,  HAYES, Sandra M.

IPC: A61K39/00 ,  A61K39/12 ,  A61P35/00

CPC classification number: A61P35/00 ,  A61K39/0011 ,  A61K39/12 ,  A61K2039/522 ,  A61K2039/523 ,  A61K2039/80 ,  C12N2710/20034 ,  C12N2770/20034 ,  A61K2300/00

Abstract: Provided herein are vaccines comprising one or more disease-associated antigenic peptides or nucleic acids encoding one or more disease-associated antigenic peptides and immunogenic compositions comprising such vaccines in combination with an inhibitor of SERPINA1, CRP, TIMP-1, or VEGF. Also provided are methods and compositions for combination therapy between immunogenic compositions, pharmaceutical compositions, and vaccines comprising such fusion polypeptides, such nucleic acids, or such recombinant bacteria or Listeria strains and an inhibitor of SERPINA1, CRP, TIMP-1, orVEGF. Also provided are methods of inducing an immune response against a disease, method of inducing an enhanced immune response against a disease, and method of increasing the overall survival rate of a subject having a disease using such vaccines and immunogenic compositions.

公开(公告)号：WO2018102585A1

公开(公告)日：2018-06-07

申请号：PCT/US2017/064016

申请日：2017-11-30

Applicant: ADVAXIS, INC. ,  PETIT, Robert ,  PERRY, Kyle ,  PRINCIOTTA, Michael F. ,  O'CONNOR, Daniel J. ,  CODER, Brandon ,  BALLI, David

Inventor： PETIT, Robert ,  PERRY, Kyle ,  PRINCIOTTA, Michael F. ,  O'CONNOR, Daniel J. ,  CODER, Brandon ,  BALLI, David

IPC: A61K35/74 ,  A61K39/00 ,  A61K48/00 ,  C12N15/74 ,  C07K14/47

CPC classification number: A61K39/0011 ,  A61K35/74 ,  A61K2039/523 ,  A61K2039/545 ,  A61K2039/55544 ,  A61K2039/55594 ,  A61K2039/64 ,  A61K2039/645 ,  C07K14/47 ,  C07K14/4746 ,  C07K14/4748 ,  C07K14/71

Abstract: 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 immune response in a subject, methods of inducing an anti-tumor or anti-cancer immune response in a subject, methods of treating a tumor or cancer in a subject, methods of preventing a tumor or cancer in a subject, and methods of protecting a subject against a tumor or cancer using such immunotherapy compositions, recombinant fusion polypeptides, nucleic acids, or recombinant bacteria or Listeria strains.

公开(公告)号：WO2016191545A1

公开(公告)日：2016-12-01

申请号：PCT/US2016/034301

申请日：2016-05-26

Applicant: ADVAXIS, INC.

Inventor： PETIT, Robert ,  PERRY, Kyle ,  PRINCIOTTA, Michael F. ,  O'CONNOR, Daniel J.

IPC: A61K48/00 ,  A61K38/16 ,  C07K14/195 ,  C12N15/74

CPC classification number: C07K14/195 ,  A61K39/0011 ,  A61K48/00 ,  A61K2039/523 ,  C12N15/62 ,  C12N2710/20034 ,  Y02A50/491 ,  Y02A50/492 ,  Y02A50/51 ,  Y02A50/53 ,  Y02A50/54 ,  Y02A50/55 ,  Y02A50/58 ,  Y02A50/60

Abstract: This invention provides a system of providing and creating personalized immunotherapeutic compositions for a subject having a disease or condition, including therapeutic immunotherapy delivery vectors and methods of making the same comprising gene expression constructs expressing peptides associated with one or more neo-epitopes or peptides containing mutations that are specific to a subject's cancer or unhealthy tissue. A delivery vector of this invention includes bacterial vectors including Listeria bacterial vectors; or viral vectors, peptide immunotherapy vectors; or DNA immunotherapy vectors, comprising one or more fusion proteins comprising one or more peptides comprising one or more neo-epitopes present in disease-bearing biological samples obtained from the subject. This invention also provides methods of using the same for inducing an immune response against a disease or condition, including a tumor or cancer, or an infection, or an autoimmune disease or an organ transplant rejection in the subject.

Abstract translation: 本发明提供了一种为具有疾病或病症的受试者提供和创造个性化的免疫治疗组合物的系统，包括治疗性免疫治疗递送载体及其制备方法，其包含表达与一个或多个新表位或肽相关的肽的基因表达构建体，其含有突变 这是特定于受试者的癌症或不健康的组织。 本发明的递送载体包括细菌载体，包括李斯特菌属细菌载体; 或病毒载体，肽免疫治疗载体; 或DNA免疫治疗载体，其包含一种或多种包含一种或多种包含存在于从受试者获得的患有疾病的生物样品中的新表位的肽的融合蛋白。 本发明还提供了使用其来诱导针对受试者中包括肿瘤或癌症，感染或自身免疫疾病或器官移植排斥的疾病或病症的免疫应答的方法。