Methods and compositions for diagnosis and treatment of B cell chronic lymphocytic leukemia
View Patent ↗Provided are isolated and purified preparations of a combination of a light chain antibody gene and a heavy chain antibody gene, where the light chain and heavy chain antibody genes are the same among more than one patient with B cell chronic lymphocytic leukemia (B-CLL). Vectors comprising those genes and cells comprising those vectors are also provided, as are isolated and purified antibodies encoded by the antibody genes. Anti-idiotype antibodies, peptides, and aptamers that bind to the antigen-binding region of an antibody encoded by the antibody genes are additionally provided, as are multimeric molecules comprising multiple binding sites that bind to the antigen-binding region of an antibody encoded by the antibody genes. Methods of determining whether a patient with B cell chronic lymphocytic leukemia (B-CLL) has a form of B-CLL that is susceptible to treatment directed to eliminating idiotype specific B cell receptor-bearing B-CLL cells are also provided, as are methods of following the progression of treatment of B-CLL in the patient. Additionally, methods of treating a patient having B-CLL are provided, as are methods of identifying a therapeutic agent for B-CLL.
1. A method of
(a) determining whether a patient with B cell chronic lymphocytic leukemia (B-CLL) has a form of B-CLL susceptible to treatment directed to eliminating idiotype-specific B cell receptor-bearing B-CLL cells, or
(b) following the progression of treatment of B-CLL in a patient having a form of B-CLL susceptible to treatment directed to eliminating idiotype-specific B cell receptor-bearing B-CLL cells,
the method comprising determining whether a B cell receptors on a B-CLL from the patient is encoded by antibody genes comprising a light chain antibody gene and a heavy chain antibody gene, wherein the light chain antibody gene and the heavy chain antibody gene are selected from the group consisting of V H 4-34/D5-5/J H 6/V L κA17/J L κ1/κ2 (Set II), V H 3-21/J H 6/V L λ3h/J L λ3 (Set III), V H 1-69/D3-16/J H 3/V L κA27/J L κ1/κ4 (Set IV), V H 1-69/D3-10/J H 6/V L λ1c/J L λ1 (Set V), V H 1-02/D6-19/J H 4/V L κO12/2/J L κ1/κ2 (Set VIa), V H 1-03/D6-19/J H 4/V L κO12/2/J L κ1/κ2 (Set VIb), V H 1-18/D6-19/J H 4/V L κO12/2/J L κ1 (Set VIc), V H 1-46/D6-19/J H 4 (Set VId), V H 5-51/D6-19/J H 4/V L κO12/2/J L κ2 (Set VIe), V H 1-69/D3-3/J H 4/V L κA19/J L κ4 (Set VII), and V H 1-69/D2-2/J H 6/V L κL6/2/J L κ3 (Set VIII),
wherein if the B cell receptor on the B-CLL cells has an idiotype encoded by the antibody genes, the patient has a form of B-CLL susceptible to treatment directed to eliminating idiotype-specific B cell receptor-bearing B-CLL cells or the treatment of the patient has not eliminated the idiotype-specific B cell receptor-bearing B-CLL cells.
2. The method of claim 1 , for determining whether a patient with B cell chronic lymphocytic leukemia (B-CLL) has a form of B-CLL susceptible to treatment directed to eliminating idiotype-specific B cell receptor-bearing B-CLL cells.
3. The method of claim 1 , for following the progression of treatment of B-CLL in a patient having a form of B-CLL susceptible to treatment directed to eliminating idiotype-specific B cell receptor-bearing B-CLL cells.
4. The method of claim 1 , wherein the light chain antibody gene and the heavy chain antibody gene is V H 4-34/D5-5/J H 6/V L κA17/J L κ1/κ2 (Set II).
5. The method of claim 1 , wherein the light chain antibody gene and the heavy chain antibody gene is V H 3-21/J H 6/V L λ3h/J L λ3 (Set III).
6. The method of claim 1 , wherein the light chain antibody gene and the heavy chain antibody gene is V H 1-69/D3-16/J H 3/V L κA27/J L κ1/κ4 (Set IV).
7. The method of claim 1 , wherein the light chain antibody gene and the heavy chain antibody gene is V H 1-69/D3-10/J H 6/V L λ1c/V L λ1 (Set V).
8. The method of claim 1 , wherein the light chain antibody gene and the heavy chain antibody gene is V H 1-02/D6-19/J H 4/V L κO12/2/J L κ1/κ2 (Set VIa).
9. The method of claim 1 , wherein the light chain antibody gene and the heavy chain antibody gene is V H 1-03/D6-19/J H 4/V L κO12/2/J L κ1/κ2 (Set VIb).
10. The method of claim 1 , wherein the light chain antibody gene and the heavy chain antibody gene is V H 1-18/D6-19/J H 4/V L κO12/2/J L κ4 (Set VIc).
11. The method of claim 1 , wherein the light chain antibody gene and the heavy chain antibody gene is V H 1-46/D6-19/J H 4 (Set VId).
12. The method of claim 1 , wherein the light chain antibody gene and the heavy chain antibody gene is V H 5-51/D6-19/J H 4/V L κO12/2/J L κ2 (Set VIe).
13. The method of claim 1 , wherein the light chain antibody gene and the heavy chain antibody gene is V H 1-69/D3-3/J H 4/V L κA19/J L κ4 (Set VII).
14. The method of claim 1 , wherein the light chain antibody gene and the heavy chain antibody gene is V H 1-69/D2-2/J H 6/V L κL6/2/J L κ3 (Set VIII).
15. The method of claim 1 , wherein the patient is pre-leukemic.
16. The method of claim 1 , wherein the patient is in an early leukemic state.
17. The method of claim 1 , wherein the patient is in a frank leukemic state.
18. The method of claim 1 , wherein the B-CLL cells from blood of the patient are evaluated.