Novel role of hematopoietic stem cells in immunologic rejection of malignant gliomas.

Published online

Journal Article

Adoptive cellular therapy (ACT) after lymphodepletive conditioning can induce dramatic clinical responses, but this approach has been largely limited to melanoma due to a lack of reliable methods for expanding tumor-specific lymphocytes from the majority of other solid cancers. We have employed tumor RNA-pulsed dendritic cells (DCs) to reliably expand CD4+ and CD8+ tumor-reactive T lymphocytes for curative ACT in a highly-invasive, chemotherapy- and radiation-resistant malignant glioma model. Curative treatment of established intracranial tumors involved a synergistic interaction between myeloablative (MA) conditioning, adoptively transferred tumor-specific T cells, and tumor RNA-pulsed DC vaccines. Hematopoietic stem cells (HSCs), administered for salvage from MA conditioning, rapidly migrated to areas of intracranial tumor growth and facilitated the recruitment of tumor-specific lymphocytes through HSC-elaborated chemokines and enhanced immunologic rejection of intracranial tumors during ACT. Furthermore, HSC transplant under non-myeloablative (NMA) conditions also enhanced immunologic tumor rejection, indicating a novel role for the use of HSCs in the immunologic treatment of malignant gliomas and possibly other solid tumors.

Full Text

Duke Authors

Cited Authors

  • Flores, C; Pham, C; Snyder, D; Yang, S; Sanchez-Perez, L; Sayour, E; Cui, X; Kemeny, H; Friedman, H; Bigner, DD; Sampson, J; Mitchell, DA

Published Date

  • March 2015

Published In

Volume / Issue

  • 4 / 3

Start / End Page

  • e994374 -

PubMed ID

  • 25949916

Pubmed Central ID

  • 25949916

International Standard Serial Number (ISSN)

  • 2162-4011

Digital Object Identifier (DOI)

  • 10.4161/2162402X.2014.994374

Language

  • eng

Conference Location

  • United States