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A cytokine cocktail directly modulates the phenotype of DC-enriched anti-tumor T cells to convey potent anti-tumor activities in a murine model.

Publication ,  Journal Article
Yang, S; Archer, GE; Flores, CE; Mitchell, DA; Sampson, JH
Published in: Cancer Immunol Immunother
November 2013

Adoptive cell transfer (ACT) using ex vivo-expanded anti-tumor T cells such as tumor-infiltrated lymphocytes or genetically engineered T cells potently eradicates established tumors. However, these two approaches possess obvious limitations. Therefore, we established a novel methodology using total tumor RNA (ttRNA) to prime dendritic cells (DC) as a platform for the ex vivo generation of anti-tumor T cells. We evaluated the antigen-specific expansion and recognition of T cells generated by the ttRNA-DC-T platform, and directly modulated the differentiation status of these ex vivo-expanded T cells with a cytokine cocktail. Furthermore, we evaluated the persistence and in vivo anti-tumor efficacy of these T cells through murine xenograft and syngeneic tumor models. During ex vivo culture, IL-2 preferentially expanded CD4 subset, while IL-7 enabled homeostatic proliferation from the original precursors. T cells tended to lose CD62L during ex vivo culture using IL-2; however, IL-12 could maintain high levels of CD62L by increasing expression on effector T cells (Tem). In addition, we validated that OVA RNA-DC only selectively expanded T cells in an antigen-specific manner. A cytokine cocktail excluding the use of IL-2 greatly increased CD62Lhigh T cells which specifically recognized tumor cells, engrafted better in a xenograft model and exhibited superior anti-tumor activities in a syngeneic intracranial model. ACT using the ex vivo ttRNA-DC-T platform in conjunction with a cytokine cocktail generated potent CD62Lhigh anti-tumor T cells and imposes a novel T cell-based therapeutic with the potential to treat brain tumors and other cancers.

Duke Scholars

Published In

Cancer Immunol Immunother

DOI

EISSN

1432-0851

Publication Date

November 2013

Volume

62

Issue

11

Start / End Page

1649 / 1662

Location

Germany

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • T-Lymphocytes
  • RNA, Neoplasm
  • Neoplasms
  • Mice, SCID
  • Mice, Knockout
  • Mice, Inbred NOD
  • Mice, Inbred C57BL
  • Mice
  • L-Selectin
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Yang, S., Archer, G. E., Flores, C. E., Mitchell, D. A., & Sampson, J. H. (2013). A cytokine cocktail directly modulates the phenotype of DC-enriched anti-tumor T cells to convey potent anti-tumor activities in a murine model. Cancer Immunol Immunother, 62(11), 1649–1662. https://doi.org/10.1007/s00262-013-1464-0
Yang, Shicheng, Gary E. Archer, Catherine E. Flores, Duane A. Mitchell, and John H. Sampson. “A cytokine cocktail directly modulates the phenotype of DC-enriched anti-tumor T cells to convey potent anti-tumor activities in a murine model.Cancer Immunol Immunother 62, no. 11 (November 2013): 1649–62. https://doi.org/10.1007/s00262-013-1464-0.
Yang S, Archer GE, Flores CE, Mitchell DA, Sampson JH. A cytokine cocktail directly modulates the phenotype of DC-enriched anti-tumor T cells to convey potent anti-tumor activities in a murine model. Cancer Immunol Immunother. 2013 Nov;62(11):1649–62.
Yang, Shicheng, et al. “A cytokine cocktail directly modulates the phenotype of DC-enriched anti-tumor T cells to convey potent anti-tumor activities in a murine model.Cancer Immunol Immunother, vol. 62, no. 11, Nov. 2013, pp. 1649–62. Pubmed, doi:10.1007/s00262-013-1464-0.
Yang S, Archer GE, Flores CE, Mitchell DA, Sampson JH. A cytokine cocktail directly modulates the phenotype of DC-enriched anti-tumor T cells to convey potent anti-tumor activities in a murine model. Cancer Immunol Immunother. 2013 Nov;62(11):1649–1662.
Journal cover image

Published In

Cancer Immunol Immunother

DOI

EISSN

1432-0851

Publication Date

November 2013

Volume

62

Issue

11

Start / End Page

1649 / 1662

Location

Germany

Related Subject Headings

  • Xenograft Model Antitumor Assays
  • T-Lymphocytes
  • RNA, Neoplasm
  • Neoplasms
  • Mice, SCID
  • Mice, Knockout
  • Mice, Inbred NOD
  • Mice, Inbred C57BL
  • Mice
  • L-Selectin