MATERIALS AND METHODS FOR DESIGNING AUTOLOGOUS IDIOTYPE VACCINES AND TREATMENT OF B-CELL MALIGNANCIES
The present invention relates to compositions, kits, and methods for preparing an autologous idiotype vaccine, or autologous anti-idiotype vaccine, for treatment of a B-cell malignancy based on the isotype(s) (class(es)) of immunoglobulins expressed by the malignancy; methods for treating B-cell malignancies; and methods for selecting a treatment for a subject having a B-cell malignancy.
1 . (canceled)
2 . A method for treating a B-cell malignancy in a subject in which the immunoglobulin isotype or isotypes exhibited by the malignancy have been predetermined, comprising administering an autologous idiotype vaccine to the subject, wherein the vaccine comprises an autologous idiotype immunoglobulin comprising at least an IgM constant region.
3 . The method of claim 2 , wherein the malignancy exhibits a predetermined immunoglobulin isotype or isotypes that is not an IgM isotype (a non-IgM immunoglobulin).
4 . The method of claim 2 , wherein the malignancy exhibits a predetermined immunoglobulin isotype or isotypes that is an IgM isotype (an IgM immunoglobulin).
5 . The method of claim 3 , wherein the non-IgM immunoglobulin is IgG, IgA, IgD, IgE, or any combination of two or more of the foregoing.
6 . The method of claim 5 , wherein the non-IgM immunoglobulin is IgG1, IgG2, IgG3, IgG4, IgA1, IgA2, IgE, IgD, or any combination of the foregoing.
7 . The method of claim 2 , wherein the vaccine comprises a chimeric idiotype immunoglobulin comprising at least an IgM constant region, and a variable region derived from a non-IgM immunoglobulin expressed by the malignancy.
8 . The method of claim 2 , wherein the vaccine comprises a chimeric idiotype immunoglobulin comprising at least an IgM constant region, and a variable region derived from an IgM immunoglobulin expressed by the malignancy.
9 . The method of claim 5 , wherein the chimeric idiotype immunoglobulin is produced recombinantly by introducing a genetic construct into a host cell, wherein the genetic construct comprises a nucleic acid sequence encoding the IgM constant region and a nucleic acid sequence encoding the variable region of the immunoglobulin expressed by the malignant cell wherein the isotype of the immunoglobulin is not IgM, and wherein the nucleic sequences are expressed by the host cell.
10 . The method of claim 9 , wherein the host cell is a mammalian cell, insect cell, bacterial cell, plant cell, viral cell, or fungal cell.
11 . The method of claim 2 , wherein the malignancy exhibits predetermined immunoglobulin isotypes that are mixed, and wherein the vaccine comprises an IgM idiotype immunoglobulin.
12 . The method of claim 2 , wherein the malignancy exhibits a predetermined immunoglobulin isotype that is only IgM, and wherein the vaccine comprises an IgM idiotype immunoglobulin.
13 . The method of claim 2 , wherein the vaccine comprises an idiotype immunoglobulin that is produced by hybridoma rescue fusion hybridization.
14 - 48 . (canceled)
49 . A method for selecting a treatment for a subject having a B-cell malignancy, comprising screening the patient for a heavy-chain isotype, wherein if the isotype has detectable M isotype, production of an autologous idiotype IgM vaccine is authorized and treatment of the subject with the autologous idiotype IgM vaccine can proceed; and
wherein if the subject has only a non-IgM B-cell malignancy, (a) production of a recombinant idiotype vaccine for the subject is authorized and treatment of the subject with the recombinant vaccine can proceed; or optionally (b) the subject is excluded from treatment with an idiotype vaccine and an alternative treatment with an alternative (non-idiotype vaccine) therapy is authorized and may proceed.
50 . The method of claim 49 , further comprising administering the autologous idiotype IgM vaccine to the subject.
51 . The method of claim 49 , further comprising administering the recombinant idiotype vaccine to the subject.
52 . The method of claim 49 , further comprising administering the alternative therapy to the subject.
53 - 78 . (canceled)
79 . An autologous idiotype vaccine comprising at least an IgM constant region.
80 . (canceled)
81 . The vaccine of claim 79 , wherein the vaccine comprises a chimeric idiotype immunoglobulin comprising at least an IgM constant region, and a variable region derived from a non-IgM immunoglobulin expressed by a B-cell malignancy.
82 . (canceled)
83 . The vaccine of claim 79 , wherein the vaccine comprises a chimeric idiotype immunoglobulin that is produced recombinantly by introducing a genetic construct into a host cell, wherein the genetic construct comprises a nucleic acid sequence encoding the IgM constant region and a nucleic acid sequence coding for the variable region of the immunoglobulin expressed by the malignant cell wherein the isotype of the immunoglobulin is not IgM, and wherein the nucleic sequences are expressed by the host cell.