Bone marrow transplantation (BMT) has shown considerable clinical benefit in a variety of hematologic diseases. Nevertheless, a significant percentage of patients will relapse following this procedure. While associated with significant immunosuppression, the BMT setting offers many advantages for the integration of vaccine strategies. Our data show highly efficient transfer of anti-tumor immunity through adoptive transfer, effective anti-tumor responses in the post-BMT prior to full immune reconstitution, and suggest a role of BMT in mediating a delay in tolerance induction. Our first protocol will integrate autologous tumor cells with a GM-CSF-producing bystander cell in the peripheral stem cell transplant setting for multiple myeloma. The trial endpoints will monitor tumor-specific responses to vaccination at various time-points either pre- or post-BMT and determine the correlation of tumor-specific responses with immune reconstitution. Critical to effective responses of GM-CSF vaccines is T cell responsiveness and T cell - antigen presenting cell (APC) interactions. We have shown that T cell tolerance is an early event in tumor progression. Overcoming this barrier offers an attractive opportunity in enhancing vaccine efficacy. The second component of this proposal focuses on the development of future strategies aimed at enhancing the T-cell and antigen presenting cell responsiveness. Integration of these findings into a clinical BMT setting could be easily accomplished and will establish the pre-clinical basis for the next generation of clinical protocols.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23CA082484-03
Application #
6647215
Study Section
Subcommittee G - Education (NCI)
Program Officer
Gorelic, Lester S
Project Start
2001-06-01
Project End
2006-05-31
Budget Start
2003-06-01
Budget End
2004-05-31
Support Year
3
Fiscal Year
2003
Total Cost
$136,788
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218