DNA vaccine containing VEGF-specific epitope and/or angiopoietin-2-specific epitope
Inventors
Nakagami, Hironori • KYUTOKU, Mariko • Morishita, Ryuichi • Tomioka, Hideki
Assignees
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Publication Number
US-10543261-B2
Publication Date
2020-01-28
Expiration Date
Abstract
The present invention provides a therapeutic or prophylactic agent for cancer, containing an expression vector encoding a chimeric Hepatitis B virus core antigen polypeptide inserted with an amino acid sequence containing a specific epitope of VEGF and/or a specific epitope of angiopoietin-2, wherein the amino acid sequence containing the specific epitope is inserted between the amino acid residues 80 and 81 of the hepatitis B virus core antigen polypeptide.
Core Innovation
The invention relates to a therapeutic or prophylactic agent for cancer comprising an expression vector encoding a chimeric Hepatitis B virus core antigen polypeptide. The chimeric HBc polypeptide is inserted with an amino acid sequence comprising a specific VEGF epitope, and the inserted sequence is located between amino acid residues 80 and 81 of the HBc polypeptide. The inserted epitope sequence comprises the amino acid sequence shown in SEQ ID NO: 1 or 2.
The approach is designed to address immune tolerance to self angiogenesis factors and to suppress tumor angiogenesis. The chimeric HBc construct predominantly induces humoral immunity, including antibody production directed against the VEGF epitope. The description further characterizes expanded epitope types for VEGF and angiopoietin-2.
The documented construct supports core-particle self-assembly as part of the DNA vaccine concept. The document also describes optional additional epitopes and spacers, and immune stimulatory sequence (CpG ISS) options in the expression vector.
Claims Coverage
Three independent claims are identified: a therapeutic or prophylactic agent claim, an expression vector for use claim, and a method of treatment or prophylaxis claim. Each independent claim centers on a VEGF epitope inserted into a chimeric HBc polypeptide at a defined position between residues 80 and 81, with the inserted epitope sequence limited to SEQ ID NO: 1 or SEQ ID NO: 2.
Therapeutic or prophylactic cancer agent with VEGF epitope-HBc insertion at residues 80-81
A therapeutic or prophylactic agent for cancer comprising an expression vector encoding a chimeric Hepatitis B virus core antigen polypeptide inserted with an amino acid sequence comprising a specific epitope of VEGF, wherein the amino acid sequence comprising the specific epitope is inserted between amino acid residues 80 and 81 of the hepatitis B virus core antigen polypeptide, and wherein the inserted amino acid sequence comprises the amino acid sequence shown in SEQ ID NO: 1 or 2.
Expression vector for treating or prophylaxis of cancer with VEGF epitope-HBc insertion at residues 80-81
An expression vector encoding a chimeric Hepatitis B virus core antigen polypeptide inserted with an amino acid sequence comprising a specific epitope of VEGF, for use in the treatment or prophylaxis of cancer, wherein the amino acid sequence comprising the specific epitope is inserted between amino acid residues 80 and 81 of the hepatitis B virus core antigen polypeptide, and wherein the inserted amino acid sequence comprises the amino acid sequence shown in SEQ ID NO: 1 or 2.
Method of treating or prophylaxis of cancer in a mammal using VEGF epitope-HBc insertion with SEQ ID-dependent mouse/human correspondence
A method for the treatment or prophylaxis of cancer in a mammal, comprising administering an effective amount of an expression vector encoding a chimeric Hepatitis B virus core antigen polypeptide inserted with an amino acid sequence comprising a specific epitope of VEGF to the mammal, wherein the amino acid sequence comprising the specific epitope is inserted between the amino acid residues 80 and 81 of the hepatitis B virus core antigen polypeptide, wherein the inserted amino acid sequence comprises the amino acid sequence shown in SEQ ID NO: 1 or 2, and wherein the expression vector is administered to a mouse when the inserted amino acid sequence comprises the amino acid sequence shown in SEQ ID NO: 1 and the expression vector is administered to a human when the inserted amino acid sequence comprises the amino acid sequence shown in SEQ ID NO: 2.
Across the independent claims, the core claim coverage is the same defined construct: an expression vector encoding a chimeric HBc polypeptide with a VEGF-specific epitope inserted between HBc residues 80 and 81, with the inserted epitope sequence limited to SEQ ID NO: 1 or 2. The method claim further ties SEQ ID NO: 1 to administration to a mouse and SEQ ID NO: 2 to administration to a human.
Stated Advantages
Suppress tumor angiogenesis while addressing immune tolerance to self angiogenesis factors.
Predominately induce humoral immunity, including antibody production directed against the VEGF epitope.
Reduce adverse influence on normal blood vessels.
Documented Applications
Treatment or prophylaxis of cancer using the described DNA vaccine/agent comprising an expression vector encoding a chimeric hepatitis B virus core antigen polypeptide with a VEGF epitope inserted between HBc residues 80 and 81.
Treatment or prophylaxis in a mammal, with SEQ ID NO: 1 indicated for administration to a mouse and SEQ ID NO: 2 indicated for administration to a human.
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