Antitumor antibodies, proteins, and uses thereof
Antibodies that bind to a 40 kDa protein which is expressed on tumors, but is not expressed on normal adult hemopoietic cells are disclosed. Also disclosed are methods for production and the use of such antibodies.
1. A method for detecting a tumor cell expressing an antigen recognized by antibody DMF10.62.3 in a subject, the method comprising:
(a) contacting the tumor cell in the subject with an isolated antibody, or antigen-binding fragment thereof, wherein the antibody is selected from the group consisting of:
(i) monoclonal antibody DMF10.62.3 produced by hybridoma cell line ATCC No. PTA-377;
(ii) a chimeric version of antibody DMF10.62.3 comprising the light and heavy chain variable regions of monoclonal antibody DMF10.62.3 and human light and heavy chain constant regions, wherein said chimeric version specifically binds to the antigen to which monoclonal antibody DMF10.62.3 binds; and
(iii) a humanized version of antibody DMF10.62.3 comprising the complementarity determining regions (CDRs) of monoclonal antibody DMF10.62.3, wherein said humanized version specifically binds to the antigen to which monoclonal antibody DMF10.62.3 binds, under conditions that enable specific binding; and
(b) detecting any specific binding of the antibody to the tumor cell, wherein binding indicates the presence of a tumor cell in the subject.
2. A method according to claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a detectable label.
3. A method according to claim 2 , wherein the detectable label is selected from the group consisting of an enzyme, streptavidin, avidin, biotin, a fluorescent material, a luminescent material, a bioluminescent material, an electron dense label, an MRI label, and a radioactive material.
4. A method for detecting a tumor cell expressing an antigen recognized by antibody DMF10.62.3 in a subject, the method comprising:
(a) contacting a tumor cell isolated from the subject with an isolated antibody, or antigen-binding fragment thereof, wherein the antibody is selected from the group consisting of:
(i) monoclonal antibody DMF10.62.3 produced by hybridoma cell line ATCC No. PTA-377;
(ii) a chimeric version of antibody DMF10.62.3 comprising the light and heavy chain variable regions of monoclonal antibody DMF10.62.3 and human light and heavy chain constant regions, wherein said chimeric version specifically binds to the antigen to which monoclonal antibody DMF10.62.3 binds; and
(iii) a humanized version of antibody DMF10.62.3 comprising the complementarity determining regions (CDRs) of monoclonal antibody DMF10.62.3, wherein said humanized version specifically binds to the antigen to which monoclonal antibody DMF10.62.3 binds, under conditions that enable specific binding; and
(b) detecting any specific binding of the antibody to the tumor cell, wherein binding indicates the presence of a tumor cell in the subject.
5. A method according to claim 3 , wherein the enzyme is horseradish peroxidase, alkaline phosphatase, β-galactosidase or acetylcholineasterase.
6. A method according to claim 3 , wherein the fluorescent material is umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin.
7. A method according to claim 3 , wherein the radioactive material is 125 I, 131 I, 35 S or 3 H.
8. A method according to claim 1 , wherein the antigen-binding fragment is an F(ab), F(ab′)2 or Fv fragment.
9. A method according to claim 2 , wherein the antigen-binding fragment is an F(ab), F(ab′)2 or Fv fragment.
10. A method according to claim 2 , wherein the tumor cell is selected from the group consisting of thymic lymphoma, a T cell tumor, a B cell lymphoma, melanoma, osteosarcoma, and acute T cell leukemia.
11. A method according to claim 2 , wherein bound antibody is detected using external scintigraphy, emission tomography or radionuclear scanning.
12. The method of claim 4 , wherein the antibody or antigen-binding fragment thereof comprises a detectable label.
13. The method of claim 12 , wherein the detectable label is selected from the group consisting of an enzyme, streptavidin, avidin, biotin, a fluorescent material, a luminescent material, a bioluminescent material, an electron dense label, an MRI label, and a radioactive material.
14. A method according to claim 13 , wherein the enzyme is horseradish peroxidase, alkaline phosphatase, β-galactosidase or acetylcholineasterase.
15. A method according to claim 13 , wherein the fluorescent material is umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin.
16. A method according to claim 13 , wherein the radioactive material is 125 I, 131 I, 35 S or 3 H.
17. A method according to claim 4 , wherein the antigen-binding fragment is an F(ab), F(ab′) 2 or Fv fragment.
18. A method according to claim 12 , wherein the antigen-binding fragment is an F(ab), F(ab′) 2 or Fv fragment.
19. A method according to claim 12 , wherein the tumor cell is selected from the group consisting of thymic lymphoma, a T cell tumor, a B cell lymphoma, melanoma, osteosarcoma, and acute T cell leukemia.