) Bone marrow transplantation for malignant disease elicits anti-tumor activity through the combined effects of the intensive chemotherapy and radiation therapy employed for conditioning the recipient and the graft versus tumor reaction associated with the transfer of allogeneic hematopoietic cells. Unfortunately, both of these therapeutic maneuvers also induce a significant immunodeficiency in the bone marrow transplant recipient. The clinical importance of the post-transplant immunodeficiency has stimulated considerable interest in devising strategies aimed at either accelerating the time required for immunologic reconstitution or at enhancing immunologic function early post-transplant. Little attention has been devoted, however, to studying tumor vaccination in the context of bone marrow transplantation. In this application, we propose to explore the ability of new vaccination strategies to enhance anti-tumor immunity in murine model systems following bone marrow transplantation. A major goal of this investigation is to determine whether anti-tumor immunity can be augmented in this setting without the concurrent exacerbation of GVHD.
The specific aims of this proposal are: 1. To characterize the biologic activity of whole tumor cell based vaccination strategies following bone marrow transplantation in murine tumor model Systems; 2. To characterize the biologic activity of tumor antigen based vaccination strategies following bone marrow transplantation in murine tumor model systems; 3. To study the potential synergistic activities of combining graft versus tumor effects with vaccination strategies following bone marrow transplantation in murine tumor model systems.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA039542-14
Application #
6318278
Study Section
Project Start
2000-06-01
Project End
2001-04-30
Budget Start
Budget End
Support Year
14
Fiscal Year
2000
Total Cost
$241,941
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215
Holtan, Shernan G; DeFor, Todd E; Panoskaltsis-Mortari, Angela et al. (2018) Amphiregulin modifies the Minnesota Acute Graft-versus-Host Disease Risk Score: results from BMT CTN 0302/0802. Blood Adv 2:1882-1888
Ortiz-Velez, Laura; Ortiz-Villalobos, Javiera; Schulman, Abby et al. (2018) Genome alterations associated with improved transformation efficiency in Lactobacillus reuteri. Microb Cell Fact 17:138
Ferrara, James L M; Chaudhry, Mohammed S (2018) GVHD: biology matters. Hematology Am Soc Hematol Educ Program 2018:221-227
Major-Monfried, Hannah; Renteria, Anne S; Pawarode, Attaphol et al. (2018) MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD. Blood 131:2846-2855
Hartwell, Matthew J; Ă–zbek, Umut; Holler, Ernst et al. (2017) An early-biomarker algorithm predicts lethal graft-versus-host disease and survival. JCI Insight 2:e89798
Stickel, N; Hanke, K; Marschner, D et al. (2017) MicroRNA-146a reduces MHC-II expression via targeting JAK/STAT signaling in dendritic cells after stem cell transplantation. Leukemia 31:2732-2741
Ferrara, James Lm; Smith, Christopher M; Sheets, Julia et al. (2017) Altered homeostatic regulation of innate and adaptive immunity in lower gastrointestinal tract GVHD pathogenesis. J Clin Invest 127:2441-2451
Miller, Holly K; Braun, Thomas M; Stillwell, Terri et al. (2017) Infectious Risk after Allogeneic Hematopoietic Cell Transplantation Complicated by Acute Graft-versus-Host Disease. Biol Blood Marrow Transplant 23:522-528
Naymagon, Steven; Naymagon, Leonard; Wong, Serre-Yu et al. (2017) Acute graft-versus-host disease of the gut: considerations for the gastroenterologist. Nat Rev Gastroenterol Hepatol 14:711-726
Renteria, Anne S; Levine, John E; Ferrara, James L M (2016) Therapeutic targets and emerging treatment options in gastrointestinal acute graft-versus-host disease. Expert Opin Orphan Drugs 4:469-484

Showing the most recent 10 out of 231 publications