NZ723750A - Compositions and methods for the treatment of her2/neu over-expressing tumors - Google Patents
Compositions and methods for the treatment of her2/neu over-expressing tumorsInfo
- Publication number
- NZ723750A NZ723750A NZ723750A NZ72375015A NZ723750A NZ 723750 A NZ723750 A NZ 723750A NZ 723750 A NZ723750 A NZ 723750A NZ 72375015 A NZ72375015 A NZ 72375015A NZ 723750 A NZ723750 A NZ 723750A
- Authority
- NZ
- New Zealand
- Prior art keywords
- recombinant
- listeria
- vaccine
- her2
- nucleic acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract 13
- 239000000203 mixture Substances 0.000 title claims abstract 3
- 206010028980 Neoplasm Diseases 0.000 title abstract 2
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 title 1
- 241000186781 Listeria Species 0.000 claims abstract 22
- 229960005486 vaccine Drugs 0.000 claims abstract 19
- 229920001184 polypeptide Polymers 0.000 claims abstract 15
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract 15
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 15
- 108020004707 nucleic acids Proteins 0.000 claims abstract 11
- 102000039446 nucleic acids Human genes 0.000 claims abstract 11
- 150000007523 nucleic acids Chemical class 0.000 claims abstract 11
- 101150029707 ERBB2 gene Proteins 0.000 claims abstract 10
- 230000002238 attenuated effect Effects 0.000 claims abstract 10
- 102000004190 Enzymes Human genes 0.000 claims abstract 8
- 108090000790 Enzymes Proteins 0.000 claims abstract 8
- 108700026244 Open Reading Frames Proteins 0.000 claims abstract 8
- 230000002503 metabolic effect Effects 0.000 claims abstract 8
- 108090000623 proteins and genes Proteins 0.000 claims abstract 7
- 239000000427 antigen Substances 0.000 claims abstract 5
- 102000036639 antigens Human genes 0.000 claims abstract 5
- 108091007433 antigens Proteins 0.000 claims abstract 5
- 201000008968 osteosarcoma Diseases 0.000 claims abstract 5
- 230000003115 biocidal effect Effects 0.000 claims abstract 3
- 210000000349 chromosome Anatomy 0.000 claims abstract 3
- 206010061289 metastatic neoplasm Diseases 0.000 claims abstract 3
- 241000282465 Canis Species 0.000 claims abstract 2
- 239000003814 drug Substances 0.000 claims abstract 2
- 238000004519 manufacturing process Methods 0.000 claims abstract 2
- 101710135803 Actin assembly-inducing protein Proteins 0.000 claims 4
- 239000002671 adjuvant Substances 0.000 claims 4
- 239000013612 plasmid Substances 0.000 claims 4
- 108010041525 Alanine racemase Proteins 0.000 claims 2
- 150000008574 D-amino acids Chemical class 0.000 claims 2
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 claims 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 claims 2
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 claims 2
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 claims 2
- 108091034117 Oligonucleotide Proteins 0.000 claims 2
- 102000004357 Transferases Human genes 0.000 claims 2
- 108090000992 Transferases Proteins 0.000 claims 2
- 239000012634 fragment Substances 0.000 claims 2
- 210000003714 granulocyte Anatomy 0.000 claims 2
- 230000002949 hemolytic effect Effects 0.000 claims 2
- 229940035032 monophosphoryl lipid a Drugs 0.000 claims 2
- 230000035772 mutation Effects 0.000 claims 2
- 210000004898 n-terminal fragment Anatomy 0.000 claims 2
- 235000018102 proteins Nutrition 0.000 claims 2
- 102000004169 proteins and genes Human genes 0.000 claims 2
- 239000001397 quillaja saponaria molina bark Substances 0.000 claims 2
- 229930182490 saponin Natural products 0.000 claims 2
- 150000007949 saponins Chemical class 0.000 claims 2
- 230000001018 virulence Effects 0.000 claims 2
- 201000008785 pediatric osteosarcoma Diseases 0.000 claims 1
- 239000003242 anti bacterial agent Substances 0.000 abstract 1
- 230000028993 immune response Effects 0.000 abstract 1
- 230000001939 inductive effect Effects 0.000 abstract 1
- 239000003550 marker Substances 0.000 abstract 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001103—Receptors for growth factors
- A61K39/001106—Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ErbB4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/74—Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
- A61K2039/522—Bacterial cells; Fungal cells; Protozoal cells avirulent or attenuated
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
- A61K2039/523—Bacterial cells; Fungal cells; Protozoal cells expressing foreign proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
- A61K2039/552—Veterinary vaccine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
- A61K2039/585—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation wherein the target is cancer
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cell Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
Abstract
This invention provides compositions and methods for treating and vaccinating against a HER2/neu antigen-expressing tumor and inducing an immune response against the same in a subject. In a specific embodiment the invention is the use of a recombinant attenuated Listeria in the manufacture of a medicament for delaying or preventing metastatic disease in a subject with a HER2/neu-expressing osteosarcoma wherein said recombinant attenuated Listeria comprises a nucleic acid molecule encoding a recombinant polypeptide, wherein said recombinant polypeptide comprises a HER2/neu chimeric antigen fused to an additional polypeptide, wherein said nucleic acid molecule comprises a first open reading frame encoding said recombinant polypeptide, wherein said nucleic acid molecule further comprises a sec-ond open reading frame encoding a metabolic enzyme, and wherein said metabolic enzyme complements an endogenous gene that is mutated in the chromosome of said recombinant Listeria strain, wherein said recombinant attenuated Listeria is to be administered as an initial vaccine, and as a first booster vaccine between 5 and 10 months after said initial vaccine, and as a second booster vaccine between 4 and 15 months after said first booster vaccine. This system does not require the use of an antibiotic resistance marker to maintain the vector encoding the recombinant polypeptide in the Listeria. The recombinant at-tenuated Listeria may also be used in a method of treating canine HER2/neu-expressing osteosarcoma.
Claims (21)
1. Use of a recombinant attenuated Listeria in the manufacture of a medicament for delaying or preventing metastatic disease in a subject with a HER2/neu-expressing osteosarcoma wherein said recombinant attenuated Listeria comprises a nucleic acid molecule encoding a recombinant polypeptide, wherein said recombinant polypeptide comprises a HER2/neu chimeric antigen fused to an additional polypeptide, wherein said nucleic acid molecule comprises a first open reading frame encoding said recombinant polypeptide, wherein said nucleic acid molecule further comprises a second open reading frame encoding a metabolic enzyme, and wherein said metabolic enzyme complements an endogenous gene that is mutated in the chromosome of said recombinant Listeria strain, wherein said recombinant attenuated Listeria is to be administered as an initial vaccine, and as a first booster vaccine between 5 and 10 months after said initial vaccine, and as a second booster vaccine between 4 and 15 months after said first booster vaccine.
2. The use of claim 1, wherein said recombinant attenuated Listeria is to be administered at of about 3.3 x 10 Listeria.
3. The use of claim 1 or 2, wherein said subject is a child, an adolescent or an adult.
4. The use of any one of claims 1 to 3, wherein said HER2/neu chimeric antigen is a human chimeric HER2/neu comprising at least 5, 9, 13, 14, or 17 of the mapped human MHC-class I epitopes.
5. The use of any one of claims 1 to 4, wherein said nucleic acid molecule is in a plasmid in said recombinant Listeria vaccine strain.
6. The use of claim 5, wherein said plasmid is stably maintained in said recombinant Listeria vaccine strain in the absence of antibiotic selection.
7. The use of any one of claims 1 to 6, wherein said recombinant Listeria comprises a mutation in the dal, the dat, and the Actin assembly-inducing protein (actA) virulence gene.
8. The use of any one of claims 1 to 7, wherein said additional polypeptide is selected from the group consisting of: a) non-hemolytic LLO protein or N-terminal fragment, b) a Proline-Glutamate-Serine-Threonine (PEST) sequence, or c) an ActA fragment.
9. The use of any one of claims 1 to 8, wherein said metabolic enzyme encoded by said second open reading frame is an alanine racemase enzyme or a D-amino acid transferase enzyme.
10. The use of any one of claims 1 to 9, further comprising an independent adjuvant.
11. The use of claim 10, wherein said adjuvant comprises a granulocyte/macrophage colony-stimulating factor (GM-CSF) protein, saponin QS21, monophosphoryl lipid A, or an unmethylated CpG-containing oligonucleotide.
12. The use of any one of claims 1 to 11, wherein said osteosarcoma is a pediatric osteosarcoma.
13. A method of delaying or preventing metastatic disease in a canine subject with a HER2/neu-expressing osteosarcoma said method comprising administering a composition comprising a recombinant attenuated Listeria comprising a nucleic acid molecule encoding a recombinant polypeptide, wherein said recombinant polypeptide comprises a HER2/neu chimeric antigen fused to an additional polypeptide, wherein said nucleic acid molecule comprises a first open reading frame encoding said recombinant polypeptide, wherein said nucleic acid molecule further comprises a second open reading frame encoding a metabolic enzyme, and wherein said metabolic enzyme complements an endogenous gene that is mutated in the chromosome of said recombinant Listeria strain, wherein said recombinant attenuated Listeria is to be administered as an initial vaccine, and as a first booster vaccine between 5 and 10 months after said initial vaccine, and as a second booster vaccine between 4 and 15 months after said first booster vaccine.
14. The method of claim 13, comprising administering about 3.3 x 10 recombinant attenuated Listeria.
15. The method of claim 13 or 14, wherein said nucleic acid molecule is in a plasmid in said recombinant Listeria vaccine strain.
16. The method of claim 15, wherein said plasmid is stably maintained in said recombinant Listeria vaccine strain in the absence of antibiotic selection.
17. The method of any one of claims 13 to 16, wherein said recombinant Listeria comprises a mutation in the dal, the dat, and the actA virulence gene.
18. The method of any one of claims 13 to 17, wherein said additional polypeptide is selected from the group consisting of: a) non-hemolytic LLO protein or N-terminal fragment, b) a Proline-Glutamate-Serine-Threonine (PEST) sequence, or c) an Actin assembly-inducing protein (ActA) fragment.
19. The method of any one of claims 13 to 18, wherein said metabolic enzyme encoded by said second open reading frame is an alanine racemase enzyme or a D-amino acid transferase enzyme.
20. The method of any one of claims 13 to 19, further comprising an independent adjuvant.
21. The method of claim 20, wherein said adjuvant comprises a granulocyte/macrophage colony-stimulating factor (GM-CSF) protein, saponin QS21, monophosphoryl lipid A, or an unmethylated CpG-containing oligonucleotide. '3f\l » pA&ti&Z «.LO- a»H«»2 112 3 1~ UQQS^m 2~Lm~LLOCMief2 3~AQX531~164
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14/189,008 US20150366955A9 (en) | 2009-11-11 | 2014-02-25 | Compositions and methods for prevention of escape mutation in the treatment of her2/neu over-expressing tumors |
| US14/268,436 US20140234370A1 (en) | 2009-11-11 | 2014-05-02 | Compositions and methods for prevention of escape mutation in the treatment of her2/neu over-expressing tumors |
| US201462076411P | 2014-11-06 | 2014-11-06 | |
| PCT/US2015/017559 WO2015130810A2 (en) | 2014-02-25 | 2015-02-25 | Compositions and methods for the treatment of her2/neu over-expressing tumors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ723750A true NZ723750A (en) | 2024-02-23 |
| NZ723750B2 NZ723750B2 (en) | 2024-05-24 |
Family
ID=
Also Published As
| Publication number | Publication date |
|---|---|
| BR112016019534A2 (en) | 2017-10-24 |
| JP2017507943A (en) | 2017-03-23 |
| AU2015223136A1 (en) | 2016-09-22 |
| EP3110942A4 (en) | 2017-08-30 |
| RU2016137834A (en) | 2018-03-29 |
| CN106661538A (en) | 2017-05-10 |
| KR20160122829A (en) | 2016-10-24 |
| SG11201607036XA (en) | 2016-09-29 |
| WO2015130810A2 (en) | 2015-09-03 |
| EP3110942A2 (en) | 2017-01-04 |
| KR20240038103A (en) | 2024-03-22 |
| MX2016011114A (en) | 2017-02-20 |
| IL247436A0 (en) | 2016-11-30 |
| CA2940646A1 (en) | 2015-09-03 |
| WO2015130810A3 (en) | 2016-01-28 |
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