The applicant has made the observation that homodimers of several anti-human B cell monoclonal antibodies (Mabs) signal significant growth arrest and/or death in lymphoma cells. Indeed, Mabs which signal poorly as (IgG) monomers make highly effective antitumor agents when they are used as (IgG-IgG) dimers. The applicant will now also study how and under what conditions Mab monomers/dimers act in conjunction with chemotherapy and immunotoxins (ITs) to give increased anti-tumor effects. She will determine whether: 1) """"""""second generation"""""""" signaling antibodies have anti-tumor activity. These include both homo- and heterodimers and new apoptosis-inducing MAbs, 2) signaling Mabs can increase the sensitivity of cells to chemotherapeutic agents plus or minus ITs; 3) her best signaling antibodies can cure SCID/Daudi mice of advanced disease when combined with chemotherapy or ITs and what the optimal way to combine these agents is. If Mabs make cells more sensitive to chemotherapy, she will determine whether lower doses of chemotherapy can be used. 4) She will also develop methods to grow primary lymphomas (from fresh patient material) in SCID mice. To this end, she is using techniques which prevent normal B cells (which contaminate lymphoma specimens) from generating lymphoproliferative disease in these animals so that the monoclonal B lymphoma cells grow out. These tumors will be used as targets for therapy. To this end, she has initiated collaborations at her institution and at two other institutions for the acquisition of fresh lymphomas.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA064679-06
Application #
6150184
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Program Officer
Yovandich, Jason L
Project Start
1994-09-30
Project End
2002-01-31
Budget Start
2000-02-01
Budget End
2001-01-31
Support Year
6
Fiscal Year
2000
Total Cost
$216,388
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
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