Immunotherapy of human neuroblastoma using umbilical cord blood-derived effector cells

Avadhut D. Joshi, Erin M. Clark, Peng Wang, Corey M. Munger, Ganapati V. Hegde, Sam Sanderson, Harish P G Dave, Shantaram S. Joshi

Research output: Contribution to journalArticle

Abstract

Tumors of the nervous system, including neuroblastoma and glioblastoma, are difficult to treat with current therapies. Despite the advances in cancer therapeutics, the outcomes in these patients remain poor and, therefore, new modalities are required. Recent literature demonstrates that cytotoxic effector cells can effectively kill tumors of the nervous system. In addition, we have previously shown that umbilical cord blood (UCB) contains precursors of antitumor cytotoxic effector cells. Therefore, to evaluate the antitumor potential of UCB-derived effector cells, studies were designed to compare the in vitro and in vivo antitumor effects of UCB- and peripheral blood (PB)-derived antigen-nonspecific and antigen-specific effector cells against tumors of the nervous system. Mononuclear cells (MNCs) from UCB were used to generate both interleukin-2 (IL-2)-activated killer (LAK) cells and tumor-specific cytotoxic T lymphocytes (CTLs). UCB-derived LAK cells showed a significant in vitro cytotoxicity against IMR-32, SK-NMC, and U-87 human neuroblastoma and glioblastoma, respectively. In addition, the CTLs generated using dendritic cells primed with IMR-32 tumor cell lysate showed a selective cytotoxicity in vitro against IMR-32 cells, but not against U-87 or MDA-231 cells. Furthermore, treatment of SCID mice bearing IMR-32 neuroblastoma with tumor-specific CTLs resulted in a significant (p <0.01) inhibition of tumor growth and increased overall survival. Thus, these results demonstrate the potential of UCB-derived effector cells against human neuroblastoma and warrant further preclinical studies.

Original languageEnglish (US)
Pages (from-to)202-212
Number of pages11
JournalJournal of NeuroImmune Pharmacology
Volume2
Issue number2
DOIs
StatePublished - Jun 2007
Externally publishedYes

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Neuroblastoma
Fetal Blood
Immunotherapy
Nervous System Neoplasms
Cytotoxic T-Lymphocytes
Neoplasms
Glioblastoma
Interleukin-2
Antigens
SCID Mice
Dendritic Cells
Therapeutics
Survival

Keywords

  • Cord blood
  • Cytotoxic T lymphocytes
  • Dendritic cells (DCs)
  • LAK cells
  • Neuroblastoma

ASJC Scopus subject areas

  • Pharmacology
  • Immunology and Allergy
  • Immunology
  • Neuroscience (miscellaneous)

Cite this

Joshi, A. D., Clark, E. M., Wang, P., Munger, C. M., Hegde, G. V., Sanderson, S., ... Joshi, S. S. (2007). Immunotherapy of human neuroblastoma using umbilical cord blood-derived effector cells. Journal of NeuroImmune Pharmacology, 2(2), 202-212. https://doi.org/10.1007/s11481-006-9038-y

Immunotherapy of human neuroblastoma using umbilical cord blood-derived effector cells. / Joshi, Avadhut D.; Clark, Erin M.; Wang, Peng; Munger, Corey M.; Hegde, Ganapati V.; Sanderson, Sam; Dave, Harish P G; Joshi, Shantaram S.

In: Journal of NeuroImmune Pharmacology, Vol. 2, No. 2, 06.2007, p. 202-212.

Research output: Contribution to journalArticle

Joshi, AD, Clark, EM, Wang, P, Munger, CM, Hegde, GV, Sanderson, S, Dave, HPG & Joshi, SS 2007, 'Immunotherapy of human neuroblastoma using umbilical cord blood-derived effector cells', Journal of NeuroImmune Pharmacology, vol. 2, no. 2, pp. 202-212. https://doi.org/10.1007/s11481-006-9038-y
Joshi, Avadhut D. ; Clark, Erin M. ; Wang, Peng ; Munger, Corey M. ; Hegde, Ganapati V. ; Sanderson, Sam ; Dave, Harish P G ; Joshi, Shantaram S. / Immunotherapy of human neuroblastoma using umbilical cord blood-derived effector cells. In: Journal of NeuroImmune Pharmacology. 2007 ; Vol. 2, No. 2. pp. 202-212.
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