Anti-CD20 combinations for treating tumors

1. A method for treating a CD20-expressing B cell lymphoma in a human subject that is in need of such treatment, comprising administering systemically to said subject a combination, comprising:

(i) an effective amount of a CD20 binding antibody; and

(ii) an effective amount of an immunotherapeutic compound, wherein the immunotherapeutic compound is resiquimod;

wherein the CD20 binding antibody and the immunotherapeutic are not covalently linked.

2. The method of claim 1 , wherein said CD20 binding antibody is rituximab, ofatumumab, veltuzumab, ocrelizumab, AME-133v, PRO131921, GA101, tositumomab, or TRU-015.

3. The method of claim 1 , further comprising administration of an effective amount of an additional therapeutic agent that is an anticancer agent.

4. The method of claim 3 , wherein said additional therapeutic agent comprises an anticancer agent that is an antimetabolite, an inhibitor of topoisomerase I and II, an alkylating agent, a microtubule inhibitor, an antiandrogen agent, a GNRh modulator or mixtures thereof, or a chemotherapeutic agent selected from the group consisting of tamoxifen, raloxifene, anastrozole, exemestane, letrozole, imatanib, paclitaxel, cyclophosphamide, lovastatin, minosine, gemcitabine, cytarabine, 5-fluorouracil, methotrexate, docetaxel, goserelin, vincristine, vinblastine, nocodazole, teniposide etoposide, gemcitabine, epothilone, vinorelbine, camptothecin, daunorubicin, actinomycin D, mitoxantrone, acridine, doxorubicin, epirubicin, and idarubicin.

5. The method of claim 1 , wherein said immunotherapeutic is of an amount that is capable of:

(1) inducing IFN-α in an enriched human blood DCs;

(2) inducing TNF-α in an enriched human blood DCs;

(3) inducing IL-12-α in an enriched human blood DCs;

(4) activating CD45+ immune cells in tumor microenvironment;

(5) activating CD4+ and CD8+ T cells in tumor microenvironment;

(6) activating NK cells in tumor microenvironment;

(7) activating plasmacytoid dendritic cells (pDC) and myeloid dendritic cells (mDc) in tumor microenvironment;

(8) activating macrophages and Monocytes in tumor microenvironment; and/or

(9) increasing migratory DCs in draining lymph nodes.

6. The method of claim 1 , wherein said B cell lymphoma is selected from the group consisting of: diffuse large B-cell lymphoma, and follicular lymphoma.

7. The method of claim 1 comprising administering to said subject a formulation comprising said immunotherapeutic in a dose of between about 0.005 mg/kg, 0.006 mg/kg, 0.007 mg/kg, 0.008 mg/kg, 0.009 mg/kg, 0.01 mg/kg, or 0.02 mg/kg, and about 0.025 mg/kg, all inclusive, twice daily, once daily, once every two, three, four, five or six days, or once, twice, or three times per week.

8. The method of claim 1 , comprising administering to said subject a formulation comprising said immunotherapeutic in a dose of between about 0.005 mg/kg, and 0.006 mg/kg, 0.007 mg/kg, 0.008 mg/kg, 0.009 mg/kg, 0.01 mg/kg, 0.02 mg/kg, or 0.025 mg/kg, all inclusive, twice daily, once daily, once every two, three, four, five or six days, or once, twice, or three times per week.

9. The method of claim 1 wherein said administration is orally, sublingually, intravenously, intramuscularly, or subcutaneously.

10. The method of claim 1 , wherein said immunotherapeutic in said subject has a local concentration that is between about 0.005 μg/ml to about 12 μg/ml.

11. The method of a claim 1 , wherein said immunotherapeutic in said subject has a local concentration that is between about 0.05 μg/ml, 0.1 μg/ml, 0.15 μg/ml, 0.2 μg/ml, 0.3 μg/ml, or 0.4 μg/ml, to about 0.5 μg/ml.