) 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.
| 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 |
| 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 |
| Hartwell, Matthew J; Özbek, 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 |
| 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 |
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