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

Nature Medicine
Yan CuiKatharine A Whartenby

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 transplantation (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.

References

Dec 15, 1991·Journal of Immunological Methods·P Matzinger
Mar 14, 1998·Proceedings of the National Academy of Sciences of the United States of America·K Staveley-O'CarrollH Levitsky
Feb 5, 1999·European Journal of Immunology·S CayeuxT Blankenstein
Feb 24, 2001·The Journal of Experimental Medicine·M V DhodapkarN Bhardwaj
Jun 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·L FongE G Engleman
Jan 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·W AsavaroengchaiJ J Mulé
Apr 20, 2002·Cancer Control : Journal of the Moffitt Cancer Center·Ivan M Borrello, Eduardo M Sotomayor

❮ Previous
Next ❯

Citations

Feb 6, 2004·Seminars in Cancer Biology·Alison M JohnRose Ann Padua
Apr 17, 2012·Journal of Biomedicine & Biotechnology·Fabian BenenciaMaria Muccioli
Mar 3, 2004·The Journal of Clinical Investigation·Katsuyoshi FurumotoMiriam Merad
Dec 18, 2013·Immunotherapy·Mario Arpinati, Antonio Curti
Feb 11, 2004·Médecine sciences : M/S·Olivier AdotéviPierre Langlade-Demoyen
Mar 28, 2008·Immunological Reviews·Martin A Cheever
Jan 5, 2005·Trends in Biotechnology·Maciej Wiznerowicz, Didier Trono
Jul 13, 2004·Seminars in Cancer Biology·Marta Coscia, Arya Biragyn
Apr 23, 2005·Immunity·Amanda MurphyMichael H Kershaw
Mar 1, 2006·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Xinchun ChenEmmanuel Katsanis
Jul 30, 2004·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·W AsavaroengchaiJ J Mulé
Nov 6, 2007·Trends in Immunology·Michele De PalmaClaire E Lewis
Mar 22, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Barbara-ann GuinnAlbert B Deisseroth
Sep 10, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Michael D MühlebachMatthias Schweizer
Dec 22, 2006·Expert Review of Vaccines·Miriam E Mossoba, Jeffrey A Medin
Aug 23, 2011·Expert Review of Vaccines·Josianne Nitcheu Tefit, Vincent Serra
Sep 18, 2014·Expert Review of Hematology·Alessandro IsidoriAntonio Curti
Nov 25, 2004·Hematology·Michael A CaligiuriIvan M Borrello
Aug 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jiali LiRonald Levy
Aug 21, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rajesh Kumar SharmaBodduluri Haribabu
Dec 24, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Theodore S NowickiAntoni Ribas
Mar 19, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Thinle ChodonAntoni Ribas

❮ Previous
Next ❯

Related Concepts

Related Feeds

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.