Abstract
A major focus of cancer immunotherapy is to develop strategies to induce T-cell responses through presentation of tumor antigens by dendritic cells (DCs). Current vaccines are limited in their ability to efficiently transfer antigens to DCs in vivo. Ex vivo - generated DCs can be efficiently loaded with antigen but after reinjection, few DCs traffic to secondary lymphoid organs, the critical sites for antigen presentation. To enhance efficiency and durability of antigen presentation by DCs, we transduced hematopoietic stem-progenitor cells (HSCs) with a model tumor antigen and then transplanted the gene-modified cells into irradiated recipient mice, which resulted in efficient expression of the transgene in a large proportion of donor derived DCs in lymphoid organs. The combination of bone marrow transplantion (BMT) using transduced HSCs, systemic agents that generate and activate DCs, and mature T-cell infusion resulted in substantial expansion and activation of antigen-specific T cells. This tripartite strategy provided potent antigen-specific immunotherapy for an aggressive established tumor.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 952-958 |
| Number of pages | 7 |
| Journal | Nature Medicine |
| Volume | 9 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2003 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Immunotherapy of established tumors using bone marrow transplantation with antigen gene-modified hematopoietic stem cells. / Cui, Yan; Kelleher, Erin; Straley, Erin; Fuchs, Ephraim; Gorski, Kevin; Levitsky, Hyam; Borrello, Ivan; Civin, Curt I.; Schoenberger, Stephen P.; Cheng, Linzhao; Pardoll, Drew M.; Whartenby, Katharine A.
In: Nature Medicine, Vol. 9, No. 7, 01.07.2003, p. 952-958.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immunotherapy of established tumors using bone marrow transplantation with antigen gene-modified hematopoietic stem cells
AU - Cui, Yan
AU - Kelleher, Erin
AU - Straley, Erin
AU - Fuchs, Ephraim
AU - Gorski, Kevin
AU - Levitsky, Hyam
AU - Borrello, Ivan
AU - Civin, Curt I.
AU - Schoenberger, Stephen P.
AU - Cheng, Linzhao
AU - Pardoll, Drew M.
AU - Whartenby, Katharine A.
PY - 2003/7/1
Y1 - 2003/7/1
N2 - A major focus of cancer immunotherapy is to develop strategies to induce T-cell responses through presentation of tumor antigens by dendritic cells (DCs). Current vaccines are limited in their ability to efficiently transfer antigens to DCs in vivo. Ex vivo - generated DCs can be efficiently loaded with antigen but after reinjection, few DCs traffic to secondary lymphoid organs, the critical sites for antigen presentation. To enhance efficiency and durability of antigen presentation by DCs, we transduced hematopoietic stem-progenitor cells (HSCs) with a model tumor antigen and then transplanted the gene-modified cells into irradiated recipient mice, which resulted in efficient expression of the transgene in a large proportion of donor derived DCs in lymphoid organs. The combination of bone marrow transplantion (BMT) using transduced HSCs, systemic agents that generate and activate DCs, and mature T-cell infusion resulted in substantial expansion and activation of antigen-specific T cells. This tripartite strategy provided potent antigen-specific immunotherapy for an aggressive established tumor.
AB - A major focus of cancer immunotherapy is to develop strategies to induce T-cell responses through presentation of tumor antigens by dendritic cells (DCs). Current vaccines are limited in their ability to efficiently transfer antigens to DCs in vivo. Ex vivo - generated DCs can be efficiently loaded with antigen but after reinjection, few DCs traffic to secondary lymphoid organs, the critical sites for antigen presentation. To enhance efficiency and durability of antigen presentation by DCs, we transduced hematopoietic stem-progenitor cells (HSCs) with a model tumor antigen and then transplanted the gene-modified cells into irradiated recipient mice, which resulted in efficient expression of the transgene in a large proportion of donor derived DCs in lymphoid organs. The combination of bone marrow transplantion (BMT) using transduced HSCs, systemic agents that generate and activate DCs, and mature T-cell infusion resulted in substantial expansion and activation of antigen-specific T cells. This tripartite strategy provided potent antigen-specific immunotherapy for an aggressive established tumor.
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UR - http://www.scopus.com/inward/citedby.url?scp=0038379169&partnerID=8YFLogxK
U2 - 10.1038/nm882
DO - 10.1038/nm882
M3 - Article
VL - 9
SP - 952
EP - 958
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 7
ER -