treatment with low dose whole body irradiation
"cure"- tumors were eradicated, did not recur and did not metastasize if I understand the article (whole article is open access under PLOS one)
ATCT= adoptive T cell transfer
Adoptive Transfer of Mammaglobin-A Epitope Specific CD8 T Cells Combined with a Single Low Dose of Total Body Irradiation Eradicates Breast Tumors
Nadine M. Lerret1, Magdalena Rogozinska1, Andrés Jaramillo2,3, Amanda L. Marzo1*
1 Rush University Medical Center, Department of Immunology and Microbiology, Chicago, Illinois, United States of America, 2 Rush University Medical Center, Department of Pathology, Chicago, Illinois, United States of America, 3 Histocompatibility Laboratory, Gift of Hope Organ & Tissue Donor Network, Itasca, Illinois, United States of America
Adoptive T cell therapy has proven to be beneficial in a number of tumor systems by targeting the relevant tumor antigen. The tumor antigen targeted in our model is Mammaglobin-A, expressed by approximately 80% of human breast tumors. Here we evaluated the use of adoptively transferred Mammaglobin-A specific CD8 T cells in combination with low dose irradiation to induce breast tumor rejection and prevent relapse. We show Mammaglobin-A specific CD8 T cells generated by DNA vaccination with all epitopes (Mammaglobin-A2.1, A2.2, A2.4 and A2.6) and full-length DNA in vivo resulted in heterogeneous T cell populations consisting of both effector and central memory CD8 T cell subsets. Adoptive transfer of spleen cells from all Mammaglobin-A2 immunized mice into tumor-bearing SCID/beige mice induced tumor regression but this anti-tumor response was not sustained long-term. Additionally, we demonstrate that only the adoptive transfer of Mammaglobin-A2 specific CD8 T cells in combination with a single low dose of irradiation prevents tumors from recurring. More importantly we show that this single dose of irradiation results in the down regulation of the macrophage scavenger receptor 1 on dendritic cells within the tumor and reduces lipid uptake by tumor resident dendritic cells potentially enabling the dendritic cells to present tumor antigen more efficiently and aid in tumor clearance. These data reveal the potential for adoptive transfer combined with a single low dose of total body irradiation as a suitable therapy for the treatment of established breast tumors and the prevention of tumor recurrence.
Citation: Lerret NM, Rogozinska M, Jaramillo A, Marzo AL (2012) Adoptive Transfer of Mammaglobin-A Epitope Specific CD8 T Cells Combined with a Single Low Dose of Total Body Irradiation Eradicates Breast Tumors. PLoS ONE 7(7): e41240. doi:10.1371/journal.pone.0041240
Editor: R. Lee Mosley, University of Nebraska Medical Center, United States of America
Received: December 5, 2011; Accepted: June 22, 2012; Published: July 20, 2012
Copyright: © 2012 Lerret et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by the Susan G. Komen for the Cure (Grant# BCTR0600731; A.L.M. and A.J.), the Prevent Cancer Foundation (A.L.M. and A.J.), the Brian Piccolo/Gavers Cancer Research Foundation (A.L.M.), and a Rush UCR grant (A.L.M.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail:
Amanda_Marzo@rush.edu
Linear Mode
