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US 12,714,733 B2Granted
Sequential heterologous boost oncolytic viral immunotherapy
AssigneesChildren's Hospital of Eastern Ontario Research Institute Inc., Iovance Biotherapeutics, Inc.
InventorsDavid Stojdl, Justyna Kmiecik, Michael F. Burgess
Life of this patent
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Abstract
The present disclosure relates to a sequential boost oncolytic viral immunotherapy and compositions for use in the same. More particularly, the disclosure relates to oncolytic viruses that significantly increase antigen-specific T cell-mediated immune responses when combined in a sequential heterologous boost treatment regimen.
Claims13
A method of treating a tumor in a subject, wherein said tumor contains at least a first tumor-specific antigen, said method comprising the steps of:
- a) administering at least one dose of a prime, said prime comprising:
- i) a first antigenic protein comprising the first tumor-specific antigen,
- ii) a vaccinia virus comprising a first nucleic acid that expresses, in the subject, the first antigenic protein comprising the first antigen, or
- iii) an adoptive cell transfer dose of antigen-specific CD8+ T cells, wherein the antigen-specific CD8+ T cells which recognize and respond to the first antigen;
- b) administering at least one dose of a first boost comprising a first oncolytic virus, said first oncolytic virus comprising a second nucleic acid that expresses, in the subject, at least a portion of said first tumor-specific antigen;
- and
- c) administering at least one dose of a second boost comprising a second oncolytic virus, said second oncolytic virus comprising a third nucleic acid that expresses, in the subject, said at least a portion of said first tumor-specific antigen, and said second oncolytic virus being immunologically distinct from said first oncolytic virus;
- wherein the order of administration in the methods is step a), followed by step b), followed by step c);
- and wherein;
- i) the first oncolytic virus is a Farmington virus and the second oncolytic virus is a Maraba MG1 virus;
- or
- ii) the first virus is a Maraba MG1 virus and the second virus is a Farmington virus.
9 more elements
A sequential heterologous boost method of inducing an immune response to a first antigen in a subject, comprising:
- a) administering to the subject a prime dose comprising:
- i) a first antigenic protein comprising the first tumor-specific antigen,
- ii) a vaccinia virus comprising a first nucleic acid that expresses, in the subject, the first antigenic protein comprising the first antigen, or
- iii) an adoptive cell transfer dose of antigen-specific CD8+ T cells, wherein the antigen-specific CD8+ T cells which recognize and respond to the first antigen;
- b) subsequently administering to the subject a dose of a first boost, wherein the first boost comprises:
- a first oncolytic virus that comprises a second nucleic acid that expresses, in the subject, the first antigen;
- and
- c) subsequently administering to the subject a dose of a second, heterologous boost, wherein the heterologous boost comprises
- a second oncolytic virus that comprises a third nucleic acid that expresses, in the subject, the first antigen;
- wherein:
- i) the first oncolytic virus is a Farmington virus and the second oncolytic virus is a Maraba MG1 virus;
- or
- ii) the first virus is a Maraba MG1 virus and the second virus is a Farmington virus.
10 more elements
A sequential heterologous boost method of inducing an immune response to at least two antigens in a subject, comprising:
- a) administering to the subject a prime dose comprising:
- i) a first antigenic protein comprising the first antigen and a second antigenic protein comprising the second antigen,
- ii) a vaccinia virus comprising a first nucleic acid that expresses, in the subject, the first antigenic protein comprising the first antigen, and a second nucleic acid that expresses, in the subject, the second antigenic protein comprising the second antigen, or
- iii) an adoptive cell transfer dose of a population of antigen-specific CD8+ T cells comprising CD8+ T cells which recognize and respond to the first antigen and CD8+ T cells which recognize and respond to the second antigen;
- b) subsequently administering to the subject a dose of a first boost, wherein the first boost comprises a first oncolytic virus that comprises:
- i) a third nucleic acid that expresses, in the subject, the first antigen, and
- ii) a fourth nucleic acid that expresses, in the subject, the second antigen;
- and
- c) subsequently administering to the subject a dose of a second, heterologous boost,
- wherein the heterologous boost comprises a second oncolytic virus that comprises:
- i) a fifth nucleic acid that expresses, in the subject, the first antigen, and
- ii) a sixth nucleic acid that expresses, in the subject, the second antigen
- wherein:
- i) the first oncolytic virus is a Farmington virus and the second oncolytic virus is a Maraba MG1 virus;
- or
- ii) the first virus is a Maraba MG1 virus and the second virus is a Farmington virus.
13 more elements
Dependencies are inferred from the claim text.