WO2004002408B1 - Cancer vaccine containing cross-species epitopes of telomerase reverse transcriptase - Google Patents
Cancer vaccine containing cross-species epitopes of telomerase reverse transcriptaseInfo
- Publication number
- WO2004002408B1 WO2004002408B1 PCT/US2003/019844 US0319844W WO2004002408B1 WO 2004002408 B1 WO2004002408 B1 WO 2004002408B1 US 0319844 W US0319844 W US 0319844W WO 2004002408 B1 WO2004002408 B1 WO 2004002408B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- protein
- tert
- human
- composition
- amino acids
- Prior art date
Links
- 108010017842 Telomerase Proteins 0.000 title claims abstract 68
- 102000004591 Telomerase Human genes 0.000 title claims abstract 68
- 238000009566 cancer vaccine Methods 0.000 title 1
- 102000004169 proteins and genes Human genes 0.000 claims abstract 58
- 108090000623 proteins and genes Proteins 0.000 claims abstract 58
- 201000011510 cancer Diseases 0.000 claims abstract 12
- 230000004044 response Effects 0.000 claims abstract 12
- 210000004027 cells Anatomy 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims 49
- 150000001413 amino acids Chemical class 0.000 claims 34
- 108020004707 nucleic acids Proteins 0.000 claims 29
- 150000007523 nucleic acids Chemical class 0.000 claims 29
- 230000000694 effects Effects 0.000 claims 11
- 239000003814 drug Substances 0.000 claims 10
- 125000003275 alpha amino acid group Chemical group 0.000 claims 8
- 238000004519 manufacturing process Methods 0.000 claims 7
- 230000001900 immune effect Effects 0.000 claims 6
- 230000002163 immunogen Effects 0.000 claims 6
- 108010057210 telomerase RNA Proteins 0.000 claims 5
- 241000701161 unidentified adenovirus Species 0.000 claims 5
- 206010028980 Neoplasm Diseases 0.000 claims 4
- 108091005810 human TERT protein Proteins 0.000 claims 4
- 102000035501 human TERT protein Human genes 0.000 claims 4
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 claims 3
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims 3
- 108010065805 Interleukin-12 Proteins 0.000 claims 3
- 108010002350 Interleukin-2 Proteins 0.000 claims 3
- 108060005135 MPL Proteins 0.000 claims 3
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 claims 3
- 241000124008 Mammalia Species 0.000 claims 2
- 230000028993 immune response Effects 0.000 claims 2
- 239000002773 nucleotide Substances 0.000 claims 2
- 125000003729 nucleotide group Chemical group 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 241000894007 species Species 0.000 claims 2
- 239000000568 immunological adjuvant Substances 0.000 claims 1
- 230000003053 immunization Effects 0.000 abstract 2
- 230000001225 therapeutic Effects 0.000 abstract 2
- 210000000987 Immune System Anatomy 0.000 abstract 1
- 206010064912 Malignant transformation Diseases 0.000 abstract 1
- 210000001744 T-Lymphocytes Anatomy 0.000 abstract 1
- 230000001093 anti-cancer Effects 0.000 abstract 1
- 230000000259 anti-tumor Effects 0.000 abstract 1
- 239000000427 antigen Substances 0.000 abstract 1
- 230000001472 cytotoxic Effects 0.000 abstract 1
- 231100000433 cytotoxic Toxicity 0.000 abstract 1
- 238000002649 immunization Methods 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 230000004565 tumor cell growth Effects 0.000 abstract 1
Abstract
It has been discovered that a robust and therapeutic anti-cancer response can be generated by immunizing with a xenogeneic form of the enzyme telomerase reverse transcriptase (TERT). Cancer subjects are multiply immunized with TERT from another species-either in protein form, or with a TERT expression vector. Presence of the xenogeneic components apparently overcomes natural immunotolerance to self-antigen. The response can be focused by simultaneous or subsequent immunization with isogenic TERT. As a result, the immune system generates T lymphocytes that are cytotoxic for virtually any cancer cell, by virtue of TERT expressed due to malignant transformation. The anti-tumor response causes a substantial inhibition of tumor cell growth, demonstrating the therapeutic benefit of this invention.
Claims
1. A method for eliciting an immune response in a human that is specific for human telomerase reverse transcriptase (TERT), comprising administering to the subject an immunogenic composition containing a protein with at least 20 consecutive amino acids of TERT of another mammalian species, or a nucleic acid encoding said protein.
2. The method of claim 1, wherein the protein comprises at least 100 consecutive amino acids of TERT of the other mammalian species.
3. The method of claim 1 , comprising administering the protein or nucleic acid to the subject on at least four different occasions.
4. The method of claim 1, further comprising subsequently administering a second composition containing a second protein with at least 20 consecutive amino acids of human TERT, or a nucleic acid encoding said second protein.
5. The method of claim 1 , which elicits a cytotoxic T cell response.
6. The method of claim 1 , wherein the protein is full-length TERT.
7. The method of claim 1 , wherein the immunogenic composition increases telomerase activity in cells surrounding the site of administration.
8. The method of claim 1, wherein the protein lacks telomerase activity when associated with telomerase RNA due to one or more changes in amino acid sequence.
9. The method of claim 1 , wherein the composition contains either: a plurality of different proteins, each comprising at least 20 consecutive amino acids of TERT from one or more non-human mammals, or one or more nucleic acids encoding said plurality of proteins.
10. The method of claim 1 , wherein the protein comprises at least 20 consecutive amino acids of any of SEQ. ID NOs:4, 6, 8, 10, and 12.
11. The method of claim 1 , wherein the composition contains an adenovirus expression vector , encoding the protein.
12. The method of claim 1 , wherein the composition also contains a factor selected from IL-12, GM-CSF, IL-2 and MPL.
23
13. An immunogenic composition formulated for human administration, comprising a protein containing at least 20 consecutive amino acids of telomerase reverse transcriptase (TERT) of a non-human mammal, or a nucleic acid encoding said protein, which upon administration to a human patient having a tumor (optionally with simultaneous or sequential administration of another TERT protein or TERT-encoding nucleic acid) elicits an immunological response against human TERT.
14. The composition of claim 13, wherein the protein comprises at least 100 consecutive amino acids of said non-human mammalian TERT.
15. A combination of pharmaceutical compositions formulated for human administration, comprising: a) a first composition comprising a protein of at least 20 consecutive amino acids of telomerase reverse transcriptase (TERT) of a non-human mammal, or a nucleic acid encoding said protein; and b) a second composition comprising a second protein of at least 20 consecutive amino acids of human TERT, or a nucleic acid encoding said second protein; wherein administration of the compositions simultaneously or sequentially to a human patient having a tumor elicits an immunological response against human TERT.
16. The composition of claim 13, wherein the TERT protein of the non-human mammal is full-length TERT.
17. The composition of claim 13, wherein the TERT protein of the non-human mammal has telomerase activity when associated with telomerase RNA component.
18. The composition of claim 13, wherein the TERT protein of the non-human mammal lacks telomerase activity due to one or more changes in amino acid sequence.
19. The composition of claim 13, either containing a plurality of different proteins, each comprising at least 20 consecutive amino acids of TERT from one or more non-human mammals, or containing one or more nucleic acids encoding said plurality of proteins.
20. The composition of claim 13, wherein the TERT protein of the non-human mammal comprises at least 20 consecutive amino acids of any of SEQ. ID NOs:4, 6, 8, 10, and 12.
21. The composition of claim 13, wherein the composition contains an adenovirus expression vector encoding the protein.
22. The composition of claim 13, wherein the composition also contains a factor selected from IL-12, GM-CSF, IL-2, and MPL.
23. The composition(s) of any of claims 13-22, packaged with information on its use for eliciting an immunological response against human TERT.
24. The composition(s) of any of claims 13-22, packaged with information on its use for treating cancer.
25. A TERT protein, comprising an amino acid sequence which is the consensus of amino acid sequences from TERT proteins from at least three different mammals.
26. The TERT protein of claim 25, comprising the sequence shown in SEQ. ID NO:12.
27. A protein comprising SEQ. ID NO:12, or fragment thereof, which has telomerase activity when complexed with telomerase RNA component.
28. A protein comprising at least 200 consecutive amino acids of SEQ. ID NO:12, incorporating one or more amino acid changes such that the protein lacks telomerase activity.
29. A plurality of proteins, each of which contains at least 20 consecutive amino acids of SEQ. ID NO:12, and which together comprise at least 200 consecutive amino acids of SEQ. ID NO:12.
30. A nucleic acid encoding the protein(s) of any of claims 26-29.
31. The nucleic acid of claim 30, which is an adenovirus expression vector.
32. The nucleic acid of claim 30, comprising at least 200 consecutive nucleotides of SEQ. ID NO:11.
33. A method for treating cancer in a human, comprising eliciting an immune response according to the method of any of claims 1-12.
34. A method for treating cancer in a human patient, comprising administering to the patient a composition or combination according to any of claims 13-22.
35. A method for treating cancer in a human patient, comprising administering to the patient the protein(s) of any of claims 25-29.
36. A method for treating cancer in a human patient, comprising administering to the patient the nucleic acid of any of claims 30-32.
25
37. An immunogenic composition formulated for human administration, comprising a protein containing at least 20 consecutive amino acids of telomerase reverse transcriptase (TERT) of a non-human mammal, or a nucleic acid encoding said protein, which upon administration to a human patient having a tumor (optionally with simultaneous or sequential administration of another TERT protein or TERT-encoding nucleic acid) elicits an immunological response against human TERT.
38. The composition of claim 37, wherein the protein comprises at least 100 consecutive amino acids of said non-human mammalian TERT.
39. The composition of either of claims 37-38, wherein the TERT protein of the non-human mammal is full-length TERT.
40. The composition of any of claims 37-39, wherein the TERT protein of the non-human mammal has telomerase activity when associated with telomerase RNA component.
41. The composition of any of claims 37-39, wherein the TERT protein of the non-human mammal lacks telomerase activity due to one or more changes in amino acid sequence.
42. The composition of any of claims 37-39, either containing a plurality of different proteins, each comprising at least 20 consecutive amino acids of TERT from one or more non-human mammals, or containing one or more nucleic acids encoding said plurality of proteins.
43. The composition of any of claims 37-42, wherein the TERT protein of the non-human mammal comprises at least 20 consecutive amino acids of any of SEQ. ID NOs:4, 6, 8, 10, and 12.
44. The composition of any of claims 37-43, wherein the composition contains an adenovirus expression vector encoding the protein.
45. The composition of any of claims 37-44, wherein the composition also contains a factor selected from IL-12, GM-CSF, IL-2, and MPL.
46. A combination of pharmaceutical compositions formulated for human administration, comprising: a) a first composition according to any of claims 37-45; and b) a second composition comprising a second protein of at least 20 consecutive amino acids of human TERT, or a nucleic acid encoding said second protein; wherein administration of the compositions simultaneously or sequentially to a human patient having a tumor elicits an immunological response against human TERT.
26
47. The composition(s) of any of claims 37-46, packaged with information on its use for eliciting an immunological response against human TERT.
48. The composition(s) of any of claims 37-47, packaged with information on its use for treating cancer.
49. A TERT protein, comprising an amino acid sequence which is the consensus of amino acid sequences from TERT proteins from at least three different mammals.
50. The TERT protein of claim 49, comprising the sequence shown in SEQ. ID NO:12.
51. A protein comprising SEQ. ID NO:12, or fragment thereof, which has telomerase activity when complexed with telomerase RNA component.
52. A protein comprising at least 200 consecutive amino acids of SEQ. ID NO:12, incorporating one or more amino acid changes such that the protein lacks telomerase activity.
53. A plurality of proteins, each of which contains at least 20 consecutive amino acids of SEQ. ID NO: 12, and which together comprise at least 200 consecutive amino acids of SEQ. ID NO: 12.
54. A nucleic acid encoding the protein(s) of any of claims 49-53.
55. The nucleic acid of claim 54, which is an adenovirus expression vector.
56. The nucleic acid of claim 54 or 55, comprising at least 200 consecutive nucleotides of SEQ. ID NO:11.
57. An immunogenic composition formulated for human administration, comprising the protein(s) of any of claims 49-53.
58. An immunogenic composition formulated for human administration, comprising the nucleic acid of any of claims 54-56.
59. Use of a protein according to any of claims 49-53, in the manufacture of a medicament for the treatment of cancer in a human.
60. Use of a nucleic acid according to any of claims 54-56, in the manufacture of a medicament for the treatment of cancer in a human.
61. Use of a protein containing at least 20 consecutive amino acids of TERT of a non-human mammal (or a nucleic acid encoding said protein) in the manufacture of a medicament for the treatment of cancer in a human.
27
62. Use of a protein containing at least 20 consecutive amino acids of TERT of a non-human mammal, or a nucleic acid encoding said protein, in the manufacture of a medicament for eliciting a cytotoxic T cell response in a human.
63. The use according to claim 61 or 62, wherein the non-human TERT protein comprises at least 20 consecutive amino acids of any of SEQ. ID NOs:4, 6, 8, 10, and 12.
64. The use according to claim 61 or 62, wherein the non-human TERT protein contains at least 100 consecutive amino acids of any of SEQ. ID NOs:4, 6, 8, 10, and 12.
65. Use of a protein containing at least 20 consecutive amino acids of human TERT, or a nucleic acid encoding said protein, in the manufacture of a medicament for the simultaneous or sequential administration to a human in combination with the composition of any of claims 37-45.
66. The use according to claim 65, wherein the human TERT protein contains at least 100 consecutive amino acids of SEQ. ID NO:2.
67. Use of a first protein containing at least 20 consecutive amino acids of TERT of a non-human mammal (or a nucleic acid encoding said protein), and a second protein containing at least 20 consecutive amino acids of human TERT (or a nucleic acid encoding said second protein) in the manufacture of a medicament or combination of medicaments for the treatment of cancer in a human.
68. Use of a first protein containing at least 20 consecutive amino acids of TERT of a non-human mammal (or a nucleic acid encoding said protein), and a second protein containing at least 20 consecutive amino acids of human TERT (or a nucleic acid encoding said second protein) in the manufacture of a medicament or combination of medicaments for eliciting a cytotoxic T cell response in a human.
69. The use according to any of claims 61-66, wherein each TERT protein lacks telomerase activity due to one or more changes in amino acid sequence.
70. The use according to any of claims 61-67, wherein the medicament(s) further comprise an immunological adjuvant.
71. A composition according to any one of claims 37-58 substantially as heretofore described with reference to any one of the examples.
72. The use according to any one of claims 59-70 substantially as heretofore described with reference to any one of the examples.
28
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002490863A CA2490863A1 (en) | 2002-06-27 | 2003-06-24 | Cancer vaccine containing cross-species epitopes of telomerase reverse transcriptase |
| AU2003249357A AU2003249357A1 (en) | 2002-06-27 | 2003-06-24 | Cancer vaccine containing cross-species epitopes of telomerase reverse transcriptase |
| EP03761998A EP1572090A4 (en) | 2002-06-27 | 2003-06-24 | Cancer vaccine containing cross-species epitopes of telomerase reverse transcriptase |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US39329502P | 2002-06-27 | 2002-06-27 | |
| US60/393,295 | 2002-06-27 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO2004002408A2 WO2004002408A2 (en) | 2004-01-08 |
| WO2004002408A3 WO2004002408A3 (en) | 2005-12-22 |
| WO2004002408B1 true WO2004002408B1 (en) | 2006-02-09 |
Family
ID=30000980
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2003/019844 WO2004002408A2 (en) | 2002-06-27 | 2003-06-24 | Cancer vaccine containing cross-species epitopes of telomerase reverse transcriptase |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20040106128A1 (en) |
| EP (1) | EP1572090A4 (en) |
| AU (1) | AU2003249357A1 (en) |
| CA (1) | CA2490863A1 (en) |
| WO (1) | WO2004002408A2 (en) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8128922B2 (en) | 1999-10-20 | 2012-03-06 | Johns Hopkins University | Superior molecular vaccine linking the translocation domain of a bacterial toxin to an antigen |
| WO2005047501A1 (en) * | 2003-02-24 | 2005-05-26 | Johns Hopkins University | Molecular vaccines employing nucleic acid encoding anti-apoptotic proteins |
| US9701725B2 (en) * | 2003-05-05 | 2017-07-11 | The Johns Hopkins University | Anti-cancer DNA vaccine employing plasmids encoding signal sequence, mutant oncoprotein antigen, and heat shock protein |
| WO2006073970A2 (en) * | 2005-01-06 | 2006-07-13 | The Johns Hopkins University | Rna interference that blocks expression of pro-apoptotic proteins potentiates immunity induced by dna and transfected dendritic cell vaccines |
| WO2008024844A2 (en) * | 2006-08-22 | 2008-02-28 | The Johns Hopkins University | Anticancer combination therapies |
| CN101522706B (en) * | 2006-10-12 | 2013-09-04 | P.安杰莱蒂分子生物学研究所 | Telomerase reverse transcriptase fusion protein, nucleotides encoding it, and uses thereof |
| US9085638B2 (en) * | 2007-03-07 | 2015-07-21 | The Johns Hopkins University | DNA vaccine enhancement with MHC class II activators |
| US20080260765A1 (en) * | 2007-03-15 | 2008-10-23 | Johns Hopkins University | HPV DNA Vaccines and Methods of Use Thereof |
| US20090285861A1 (en) * | 2008-04-17 | 2009-11-19 | Tzyy-Choou Wu | Tumor cell-based cancer immunotherapeutic compositions and methods |
| EP2424990A4 (en) * | 2009-04-28 | 2013-05-15 | Univ Johns Hopkins | Compositions and methods for enhancing antigen-specific immune responses |
| JP6042211B2 (en) | 2010-02-16 | 2016-12-14 | ウルティモバックス エーエス | Polypeptide |
| EP2639299A1 (en) | 2012-03-16 | 2013-09-18 | Invectys | Universal cancer peptides derived from telomerase |
| CA2898126A1 (en) * | 2013-03-15 | 2014-09-18 | The Trustees Of The University Of Pennsylvania | Cancer vaccines and methods of treatment using the same |
| EP3449936A1 (en) | 2013-03-28 | 2019-03-06 | Invectys | A cancer vaccine for cats |
| DK2978444T3 (en) * | 2013-03-28 | 2019-03-18 | Invectys | CANCERVACCINE FOR DOGS |
| RS60232B1 (en) | 2013-10-28 | 2020-06-30 | Invectys | A telomerase encoding dna vaccine |
| BR112016008807B1 (en) * | 2013-10-28 | 2021-07-06 | Invectys | use of a nucleic acid |
| KR20220024974A (en) | 2016-09-30 | 2022-03-03 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | Tert immunogenic compositions and methods of treatment using the same |
| EP3622078A1 (en) | 2017-05-09 | 2020-03-18 | Invectys | Recombinant measles vaccine expressing htert |
| EP3494987A1 (en) * | 2017-12-11 | 2019-06-12 | Fraunhofer Gesellschaft zur Förderung der Angewand | Compositions for the treatment or prevention of neurodegenerative disorders, in particular parkinson`s disease |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6261836B1 (en) * | 1996-10-01 | 2001-07-17 | Geron Corporation | Telomerase |
| WO1999027113A1 (en) * | 1997-11-26 | 1999-06-03 | Geron Corporation | Mouse telomerase reverse transcriptase |
| AU761567B2 (en) * | 1999-02-04 | 2003-06-05 | Geron Corporation | Replicative virus driven by the promoter for telomerase reverse transcriptase for use in treating cancer |
| WO2003038047A2 (en) * | 2001-10-29 | 2003-05-08 | Baylor College Of Medicine | Human telomerase reverse transcriptase as a class-ii restricted tumor-associated antigen |
-
2003
- 2003-06-24 US US10/602,441 patent/US20040106128A1/en not_active Abandoned
- 2003-06-24 CA CA002490863A patent/CA2490863A1/en not_active Abandoned
- 2003-06-24 EP EP03761998A patent/EP1572090A4/en not_active Withdrawn
- 2003-06-24 WO PCT/US2003/019844 patent/WO2004002408A2/en not_active Application Discontinuation
- 2003-06-24 AU AU2003249357A patent/AU2003249357A1/en not_active Abandoned
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2004002408B1 (en) | Cancer vaccine containing cross-species epitopes of telomerase reverse transcriptase | |
| RU2642300C2 (en) | Immunotherapeutic compositions on the basis of yeast-muc1 and methods of their use | |
| AU2005232396B2 (en) | Vaccination against malignant melanoma using BCG and/or vaccinia | |
| ES2373055T3 (en) | ANTIQUE PENCIL OF CANCER REJECTION DERIVED FROM GLIPICAN-3 (GPC3) FOR USE IN PATIENTS POSITIVE TO HLA-A2 AND PHARMACEUTICAL PRODUCT THAT INCLUDES THE ANTIGEN. | |
| HUE033491T2 (en) | Yeast-brachyury immunotherapeutic compositions | |
| EP2736527A1 (en) | Dendritic cell (dc)-vaccine therapy for pancreatic cancer | |
| ES2398492T3 (en) | Fusion proteins comprising the tumor rejection antigens NY-ESO-1 and LAGE-1 | |
| RU2385163C2 (en) | Preventive cancer vaccine | |
| US8309096B2 (en) | Fusion protein | |
| WO1993022341A1 (en) | Synthetic peptide vaccines for dental caries | |
| CN110167576A (en) | The synthesis for targeting the optimization of fibroblast activation protein shares immunogenic composition | |
| EP2112160B1 (en) | Immunotherapeutic formulations to generate autoantibodies capable to avoid the binding of interleukin-2 to its receptor. Their use in the treatment of cancer | |
| JP3876162B2 (en) | Methods and compositions for the treatment of hepatocellular carcinoma | |
| AU2002304165B9 (en) | Polynucleotide vaccine | |
| JPH11512076A (en) | Compositions exhibiting ADP-ribosyltransferase activity and methods for their preparation and use | |
| JPWO2009001673A1 (en) | ATP-containing immune adjuvant | |
| JP2005247861A (en) | Mucin peptide having immuno-enhancing characteristic | |
| US20090246213A1 (en) | Vaccine comprising a polynucleotide encoding an antigen recognized by a cd4+ helper t-cell and a polynucleotide encoding a tumor specific or associated antigen recognized by a cd8+ ctl | |
| Sabel et al. | Immunologic approaches to breast cancer treatment | |
| US20090252751A1 (en) | Immune adjuvant comprising ubiquinone | |
| EA006743B1 (en) | Thymosin augmentation of genetic immunization | |
| CN116783221A (en) | Chimeric antigens comprising the extracellular domain of PD-L1 | |
| CN113318225A (en) | Tumor immunopotentiator and its preparation method and application | |
| Simerska et al. | Liposaccharides in Peptide Vaccine Delivery | |
| BR112014003477B1 (en) | IMMUNOTHERAPEUTIC COMPOSITION OF YEAST MUC1 |