Using current chemotherapies, the majority of patients with B cell non- Hodgkin's lymphoma (NHL) will die of their disease. Immunologic approaches to NHL offer the possibility of enhancing chemotherapeutic responses. Anti-idiotypic antibodies, unlabeled monoclonal antibodies and antibodies conjugated to toxins or radio-isotopes have shown promise although transient responses, inefficiency of killing, or toxicity limit their application in the clinical setting. A method to enhance target cell destruction without toxicity while retaining the specificity of monoclonal antibody therapy would have great therapeutic potential particularly for those patients who could not tolerate additional toxicity. Bispecific antibodies (BsAbs) provide a method to harness effector cells and re-direct cytotoxicity to a malignant cell target while minimizing systemic toxicity We have shown in vitro that BsAb armed macrophages can efficiently kill malignant B cells. The bispecific antibodies used in these experiments have affinity for CD37, expressed on the majority of NHL B cells, and the Ig Fc receptor (CD64) found on monocytes/macrophages. We propose, in this submission, to construct and purify clinical grade bispecific antibody using H22 (anti-CD64) and MB-1 (anti-CD37) and perform all necessary pre clinical evaluations on this antibody in anticipation of a phase I clinical trial.

Proposed Commercial Applications

Therapy and potential vaccine for non- Hodgkin's lymphoma.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Technology Transfer (STTR) Grants - Phase II (R42)
Project #
5R42CA071117-03
Application #
6173271
Study Section
Special Emphasis Panel (ZRG1-SSS-1 (02))
Program Officer
Wu, Roy S
Project Start
1996-09-30
Project End
2002-04-30
Budget Start
2000-05-01
Budget End
2002-04-30
Support Year
3
Fiscal Year
2000
Total Cost
$243,750
Indirect Cost
Name
Medarex, Inc.
Department
Type
DUNS #
City
Princeton
State
NJ
Country
United States
Zip Code
08540