Sustained expansion of NKT cells and antigen-specific T cells after injection of α-galactosyl-ceramide loaded mature dendritic cells in cancer patients Journal Article
| Authors: | Chang, D. H.; Osman, K.; Connolly, J.; Kukreja, A.; Krasovsky, J.; Pack, M.; Hutchinson, A.; Geller, M.; Liu, N.; Annable, R.; Shay, J.; Kirchhoff, K.; Nishi, N.; Ando, Y.; Hayashi, K.; Hassoun, H.; Steinman, R. M.; Dhodapkar, M. V. |
| Article Title: | Sustained expansion of NKT cells and antigen-specific T cells after injection of α-galactosyl-ceramide loaded mature dendritic cells in cancer patients |
| Abstract: | Natural killer T (NKT) cells are distinct glycolipid reactive innate lymphocytes that are implicated in the resistance to pathogens and tumors. Earlier attempts to mobilize NKT cells, specifically, in vivo in humans met with limited success. Here, we evaluated intravenous injection of monocyte-derived mature DCs that were loaded with a synthetic NKT cell ligand, α-galactosyl-ceramide (α-GalCer; KRN-7000) in five patients who had advanced cancer. Injection of α-GalCer-pulsed, but not unpulsed, dendritic cells (DCs) led to >100-fold expansion of several subsets of NKT cells in all patients; these could be detected for up to 6 mo after vaccination. NKT activation was associated with an increase in serum levels of interleukin-12 p40 and IFN-γ inducible protein-10. In addition, there was an increase in memory CD8+ T cells specific for cytomegalovirus in vivo in response to α-GalCer-loaded DCs, but not unpulsed DCs. These data demonstrate the feasibility of sustained expansion of NKT cells in vivo in humans, including patients who have advanced cancer, and suggest that NKT activation might help to boost adaptive T cell immunity in vivo. |
| Keywords: | adult; clinical article; aged; human cell; clinical trial; side effect; cancer patient; flow cytometry; neoplasms; cell proliferation; lymphocyte proliferation; t lymphocyte; cd8-positive t-lymphocytes; blood chemical analysis; cancer immunotherapy; liver toxicity; dendritic cell; lymphocyte activation; cytokines; dendritic cells; cellular immunity; immunotherapy; reverse transcriptase polymerase chain reaction; vaccination; cytotoxic t lymphocyte; natural killer cell; killer cells, natural; malignant neoplastic disease; tumor immunity; cytokine production; open study; antinuclear antibody; gamma interferon inducible protein 10; memory cell; autoimmune disease; cytomegalovirus; chemokines; partial thromboplastin time; alpha galactosylceramide; interleukin 12p40; interleukin-12; galactosylceramides; chemokines, cxc; rheumatoid factor; 1 o (alpha galactopyranosyl) 2 hexacosanoylamino 1,3,4 octadecanetriol |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 201 |
| Issue: | 9 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2005-05-02 |
| Start Page: | 1503 |
| End Page: | 1517 |
| Language: | English |
| DOI: | 10.1084/jem.20042592 |
| PUBMED: | 15867097 |
| PROVIDER: | scopus |
| PMCID: | PMC1389847 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 177" - "Export Date: 24 October 2012" - "CODEN: JEMEA" - "Source: Scopus" |
