초록 ▼

The present invention provides a monoclonal anti-idiotype antibody 11D10 that elicits an immune response against a specific epitope of a high molecular weight mucin of human milk fat globule (HMFG) and a hybridoma that produces 11D10. The hybridoma that produces 11D10 was selected by specific proced

The present invention provides a monoclonal anti-idiotype antibody 11D10 that elicits an immune response against a specific epitope of a high molecular weight mucin of human milk fat globule (HMFG) and a hybridoma that produces 11D10. The hybridoma that produces 11D10 was selected by specific procedures. 11D10 induces an immunological response to HMFG in nice, rabbits, monkeys and patients with advanced HMFG-associated tumors. This invention provides compositions derived from polynucleotide sequences encoding the variable light and/or variable heavy regions of monoclonal anti-idiotype antibody 11D10, as well as polypeptides encoded thereby. The invention also provides compositions which can be used in the detection or treatment of HMFG-associated tumors.

대표청구항 ▼

1. An isolated monoclonal anti-idiotype antibody 11D10 produced by hybridoma cell line ATCC No. HB 12020.2. A labeled antibody comprising the antibody of claim 1, further comprising a wherein said label is capable of producing a detectable signal.3. A composition comprising the anti-idiotype antibod

1. An isolated monoclonal anti-idiotype antibody 11D10 produced by hybridoma cell line ATCC No. HB 12020.2. A labeled antibody comprising the antibody of claim 1, further comprising a wherein said label is capable of producing a detectable signal.3. A composition comprising the anti-idiotype antibody of claim 1 and a pharmaceutically acceptable excipient.4. A method for promoting clearance of a labeled anti-human milk fat globule (HMFG) antibody that binds to the antibody of claim 1 from the circulation or tissues of an individual who has received the labeled anti-HMFG antibody, comprising administering monoclonal the antibody of claim 1 to the individual.5. A method for detecting an anti-human milk fat globule immunological response in an individual comprising the steps of (a) contacting a biological sample from the individual with the monoclonal anti-idiotype antibody 11D10 of claim 1 under conditions that permit formation of a stable complex between the monoclonal anti-idiotype antibody and an antibody containing the paratope of the monoclonal anti-idiotype antibody; and (b) detecting any of the complexes formed, wherein the presence of the complexes is indicative of the presence of an anti-human milk fat globule immunological response in the individual.6. A composition comprising an effective amount of the anti-idiotype antibody of claim 1, wherein an effective amount is an amount sufficient to elicit an anti-human milk fat globule immune response.7. An immunogenic composition comprising the anti-idiotype antibody of claim 1 and a pharmaceutically acceptable excipient.8. The immunogenic composition of claim 7, further comprising an adjuvant.9. A method of eliciting an immune response in an individual with advanced human milk fat globule associated disease comprising the step of administering an effective amount of the immunogenic composition of claim 8 to the individual.10. A method of eliciting an immune response in an individual with advanced human milk fat globule associated disease comprising the step of administering an effective amount of the anti-idiotype antibody of claim 1 to the individual.11. The method of claim 10, wherein the advanced human milk fat globule associated disease is breast cancer.12. A kit comprising the anti-idiotype antibody of claim 1 in suitable packaging.13. The kit of claim 12, wherein the antibody comprises a detectable label.14. A hybridoma cell line designated ATCC No. HB 12020.15. A hybridoma having all the identifying characteristics of a cell of the hybridoma cell line according to claim 14.16. A purified antibody having all the identifying characteristics of antibody produced by a hybridoma cell line according to claim 14.17. A composition comprising an effective amount of the antibody of claim 16, wherein an effective amount is an amount sufficient to elicit an anti-human milk fat globule immune response.18. The purified antibody of claim 16, said antibody comprising the sequence of SEQ ID NO:2.19. The purified antibody of claim 16, said antibody comprising the sequence of SEQ ID NO:4.20. A composition comprising the purified antibody of claim 16 and a pharmaceutically acceptable excipient.21. A composition according to claim 20, wherein the composition is immunogenic.22. A composition according to claim 21, further comprising an adjuvant.23. A polypeptide having immunological activity of anti-idiotype antibody 11D10, wherein the polypeptide comprises an immunoglobulin variable region containing three light chain complementarity determining regions (CDRs) of anti-idiotype antibody 11D10, and an immunoglobulin variable region containing three heavy chain CDRs of anti-idiotype antibody 11D10, wherein anti-idiotype antibody 11D10 is produced by the hybridoma cell line designated ATCC No. HB 12020, and wherein the immunological activity of the polypeptide is an ability to stimulate a specific immune response against human milk fat globule (HMFG).24. The polypeptide of claim 23, wherein the light chain variable region amino acid sequence is contained in SEQ ID NO:2 and the heavy chain variable region amino acid sequence is contained in SEQ ID NO:4.25. The polypeptide of claim 23, wherein the polypeptide contains a sequence of at least 2 contiguous amino acids which are identical in forward or reverse orientation to 2 contiguous amino acids of a sequence in human mucin from human milk fat globule (HMFG), wherein said HMFG sequence is contained in SEQ ID NO:33.26. A polymeric 11D10 polypeptide comprising a plurality of the polypeptide of claim 23.27. A kit comprising the polypeptide of claim 23 in suitable packaging.28. A composition comprising an effective amount of the polypeptide of claim 23, wherein an effective amount is an amount sufficient to elicit an anti-human milk fat globule immune response.29. A composition comprising the polypeptide of claim 23 and a pharmaceutically acceptable excipient.30. A method of eliciting an immune response in an individual with advanced human milk fat globule associated disease comprising the step of administering an effective amount of a polypeptide according to claim 23 to the individual.31. The polypeptide of claim 23, wherein the specific immune response comprises production of HMFG-specific antibodies.32. The polypeptide of claim 23, wherein the specific immune response comprises production of HMFG-specific T cells.33. An immunogenic composition comprising the polypeptide of claim 23 and a pharmaceutically acceptable excipient.34. The immunogenic composition of claim 33, further comprising an adjuvant.35. A fusion polypeptide comprising the polypeptide of claim 23.36. A fusion polypeptide according to claim 35, wherein the amino acid sequences of the light chain variable region and the heavy chain variable region are contained in SEQ ID NO:2 and SEQ ID NO:4, respectively.37. The fusion polypeptide of claim 35 further comprising a cytokine.38. The fusion polypeptide of claim 37, wherein the cytokine is granulocyte macrophage colony stimulating factor.39. The fusion polypeptide of claim 37, wherein the cytokine is interleukin 2.40. The fusion polypeptide of claim 35, wherein the immunoglobulin variable region of the polypeptide of claim 20, containing three CDRs from the light chain variable region of anti-idiotype antibody 11D10, and the immunoglobulin variable region of the polypeptide of claim 20, containing three CDRs from the heavy chain variable region of anti-idiotype antibody 11D10, are linked by a linker polypeptide of about 5 to 20 amino acids.41. A fusion polypeptide according to claim 40, wherein the linker polypeptide comprises the amino acid sequence (GGGGS)3 (SEQ ID NO:35).42. The fusion polypeptide of claim 35, comprising the light chain variable region and the heavy chain variable region of anti-idiotype antibody 11D10, wherein the light chain variable region and the heavy chain variable region are contained in SEQ ID NO:2 and SEQ ID NO:4, respectively.43. The fusion polypeptide of claim 42, wherein the light chain variable region and the heavy chain variable region are joined by a linker polypeptide of about 5 to 20 amino acids.44. The fusion polypeptide of claim 35 further comprising a heterologous immunoglobulin constant region.45. The fusion polypeptide of claim 44, wherein the immunoglobulin constant region is human.46. A humanized antibody comprising three CDRs from the light chain variable region of antibody 11D10, three CDRs from the heavy chain variable region of antibody 11D10, and a constant region that is a human sequence, wherein antibody 11D10 is produced by the hybridoma cell line designated ATCC No. HB 12020, and wherein the humanized antibody is able to stimulate a specific immune response against human milk fat globule (HMFG).47. The humanized antibody of claim 46, wherein the specific immune response comprises production of HMFG-specific antibody.48. The humanized antibody of claim 46, wherein the specific immune response comprises production of HMFG-specific T cells.49. The humanized antibody of claim 46, wherein the framework regions are human sequences.50. A humanized antibody according to claim 46, wherein the light chain variable region of antibody 11D10 and the heavy chain variable region of antibody 11D10 are contained in SEQ ID NO:2 and SEQ ID NO:4, respectively.51. A composition comprising the humanized antibody of claim 46 and a pharmaceutically acceptable excipient.52. A method of eliciting an immune response in an individual with advanced human milk fat globule associated disease comprising the step of administering an effective amount of an antibody according to claim 46 to the individual.53. A composition according to claim 51, wherein the composition is immunogenic.54. A composition according to claim 53 further comprising an adjuvant.55. A composition comprising a pharmaceutically acceptable excipient and a polypeptide having immunological activity of anti-idiotype antibody 11D10, wherein the polypeptide comprises an immunoglobulin variable region containing three light chain complementarity determining regions (CDRs) of anti-idiotype antibody 11D10, and an immunoglobulin variable region containing three heavy chain CDRs of anti-idiotype antibody 11D10, wherein anti-idiotype antibody 11D10 is produced by the hybridoma cell line designated ATCC No. HB 12020, and wherein the immunological activity of the polypeptide is an ability to stimulate a specific immune response against human milk fat globule (HMFG).56. The composition of claim 55, wherein the specific immune response comprises production of HMFG-specific antibody.57. The composition of claim 55, wherein the specific immune response comprises production of HMFG-specific T cells.58. A humanized antibody comprising three CDRs from the light chain variable region of antibody 11D10, three CDRs from the heavy chain variable region of antibody 11D10, and framework regions that are human sequences, wherein antibody 11D10 is produced by the hybridoma cell line designated ATCC No. HB 12020, and wherein the humanized antibody is able to stimulate a specific immune response against human milk fat globule (HMFG).59. A method of eliciting an immune response in an individual with advanced human milk fat globule associated disease comprising the step of administering an effective amount of an antibody according to claim 58 to the individual.60. A humanized antibody comprising three CDRs from the light chain variable region of antibody 11D10, three CDRs from the heavy chain variable region of antibody 11D10, and framework regions that are human sequences, wherein antibody 11D10 is produced by the hybridoma cell line designated ATCC No. HB 12020, wherein the humanized antibody is able to stimulate a specific immune response against human milk fat globule (HMFG), and wherein the light chain variable region of antibody 11D10 and the heavy chain variable region of antibody 11D10 are contained in SEQ ID NO:2 and SEQ ID NO:4, respectively.61. A method of eliciting an immune response in an individual with advanced human milk fat globule associated disease comprising the step of administering an effective amount of an antibody according to claim 60 to the individual.62. A composition comprising the humanized antibody of claim 60 and a pharmaceutically acceptable excipient.63. A composition according to claim 62, wherein the composition is immunogenic.64. A composition according to claim 63, further comprising an adjuvant.65. An antibody comprising a light chain variable region amino acid sequence contained in SEQ ID NO:2 and a heavy chain variable region amino acid sequence contained in SEQ ID NO:4, wherein the antibody is able to stimulate a specific immune response against human milk fat globule (HMFG).66. A composition comprising the antibody of claim 65 and a pharmaceutically acceptable excipient.67. A composition according to claim 66, wherein the composition is immunogenic.68. A composition according to claim 67, further comprising an adjuvant.69. An isolated antibody comprising three CDRs from the light chain variable region of anti-idiotype antibody 11D10 and three CDRs from the heavy chain variable region of anti-idiotype antibody 11D10, wherein anti-idiotype antibody 11D10 is produced by the hybridoma cell line designated ATCC No. HB 12020, wherein the CDRs from the light chain variable region are contained in SEQ ID NO:2 and the CDRs from the heavy chain variable region are contained in SEQ ID NO:4, and wherein the antibody is able to stimulate a specific immune response against human milk fat globule (HMFG).70. A method of eliciting an immune response in an individual with advanced human milk fat globule associated disease comprising the step of administering an effective amount of an antibody according to claim 69 to the individual.71. A composition comprising the antibody of claim 69 and a pharmaceutically acceptable excipient.72. A composition according to claim 71, wherein the composition is immunogenic.73. A composition according to claim 72, further comprising an adjuvant.74. A polypeptide comprising an immunoglobulin variable region containing three light chain complementarity determining regions (CDRs) of antibody 11D10, or an immunoglobulin variable region containing three heavy chain CDRs of antibody 11D10, wherein antibody 11 D10 is produced by a hybridoma cell line designated ATCC NO. HB 12020.75. A composition comprising the polypeptide of claim 74 and a pharmaceutically acceptable excipient.76. A polypeptide according to claim 74, comprising an immunoglobulin variable region containing the three light chain CDRs of antibody 11D10.77. A polypeptide according to claim 74, comprising an immunoglobulin variable region containing the three heavy chain CDRs of antibody 11D10.78. A polypeptide according to claim 74, wherein the light chain variable region is contained in SEQ ID NO:2.79. A polypeptide according to claim 74, wherein the heavy chain variable region is contained in SEQ ID NO:4.80. A polypeptide comprising an immunoglobulin variable region containing three light chain complementarity determining regions (CDRs) of antibody 11D10 and an immunoglobulin variable region containing three heavy chain CDRs of antibody 11D10, wherein antibody 11D10 is produced by a hybridoma cell line designated ATCC NO. HB 12020, and wherein the light and heavy chain variable region sequences are contained in SEQ ID NO:2 and SEQ ID NO:4, respectively, and wherein the antibody is able to stimulate a specific immune response against human milk fat globule (HMFG).81. A method of eliciting an immune response in an individual with advanced human milk fat globule associated disease comprising thee step of administering an effective amount of a polypeptide according to claim 80 to the individual.