Immunotherapy of established tumors using bone marrow transplantation with antigen gene-modified hematopoietic stem cells

Yan Cui, Erin Kelleher, Erin Straley, Ephraim Fuchs, Kevin Gorski, Hyam Levitsky, Ivan Borrello, Curt I. Civin, Stephen P. Schoenberger, Linzhao Cheng, Drew M. Pardoll, Katharine A. Whartenby

Research output: Contribution to journalArticle

49 Scopus citations

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 languageEnglish (US)
Pages (from-to)952-958
Number of pages7
JournalNature Medicine
Volume9
Issue number7
DOIs
StatePublished - Jul 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Cui, Y., Kelleher, E., Straley, E., Fuchs, E., Gorski, K., Levitsky, H., Borrello, I., Civin, C. I., Schoenberger, S. P., Cheng, L., Pardoll, D. M., & Whartenby, K. A. (2003). Immunotherapy of established tumors using bone marrow transplantation with antigen gene-modified hematopoietic stem cells. Nature Medicine, 9(7), 952-958. https://doi.org/10.1038/nm882