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Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses.

Publication ,  Journal Article
Huang, M-N; Nicholson, LT; Batich, KA; Swartz, AM; Kopin, D; Wellford, S; Prabhakar, VK; Woroniecka, K; Nair, SK; Fecci, PE; Sampson, JH; Gunn, MD
Published in: J Clin Invest
February 3, 2020

Efficacy of dendritic cell (DC) cancer vaccines is classically thought to depend on their antigen-presenting cell (APC) activity. Studies show, however, that DC vaccine priming of cytotoxic T lymphocytes (CTLs) requires the activity of endogenous DCs, suggesting that exogenous DCs stimulate antitumor immunity by transferring antigens (Ags) to endogenous DCs. Such Ag transfer functions are most commonly ascribed to monocytes, implying that undifferentiated monocytes would function equally well as a vaccine modality and need not be differentiated to DCs to be effective. Here, we used several murine cancer models to test the antitumor efficacy of undifferentiated monocytes loaded with protein or peptide Ag. Intravenously injected monocytes displayed antitumor activity superior to DC vaccines in several cancer models, including aggressive intracranial glioblastoma. Ag-loaded monocytes induced robust CTL responses via Ag transfer to splenic CD8+ DCs in a manner independent of monocyte APC activity. Ag transfer required cell-cell contact and the formation of connexin 43-containing gap junctions between monocytes and DCs. These findings demonstrate the existence of an efficient gap junction-mediated Ag transfer pathway between monocytes and CD8+ DCs and suggest that administration of tumor Ag-loaded undifferentiated monocytes may serve as a simple and efficacious immunotherapy for the treatment of human cancers.

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

February 3, 2020

Volume

130

Issue

2

Start / End Page

774 / 788

Location

United States

Related Subject Headings

  • Neoplasms, Experimental
  • Monocytes
  • Mice, Knockout
  • Mice
  • Immunotherapy
  • Immunology
  • Immunity, Cellular
  • CD8-Positive T-Lymphocytes
  • Antigens, Neoplasm
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Huang, M.-N., Nicholson, L. T., Batich, K. A., Swartz, A. M., Kopin, D., Wellford, S., … Gunn, M. D. (2020). Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses. J Clin Invest, 130(2), 774–788. https://doi.org/10.1172/JCI128267
Huang, Min-Nung, Lowell T. Nicholson, Kristen A. Batich, Adam M. Swartz, David Kopin, Sebastian Wellford, Vijay K. Prabhakar, et al. “Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses.J Clin Invest 130, no. 2 (February 3, 2020): 774–88. https://doi.org/10.1172/JCI128267.
Huang M-N, Nicholson LT, Batich KA, Swartz AM, Kopin D, Wellford S, et al. Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses. J Clin Invest. 2020 Feb 3;130(2):774–88.
Huang, Min-Nung, et al. “Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses.J Clin Invest, vol. 130, no. 2, Feb. 2020, pp. 774–88. Pubmed, doi:10.1172/JCI128267.
Huang M-N, Nicholson LT, Batich KA, Swartz AM, Kopin D, Wellford S, Prabhakar VK, Woroniecka K, Nair SK, Fecci PE, Sampson JH, Gunn MD. Antigen-loaded monocyte administration induces potent therapeutic antitumor T cell responses. J Clin Invest. 2020 Feb 3;130(2):774–788.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

February 3, 2020

Volume

130

Issue

2

Start / End Page

774 / 788

Location

United States

Related Subject Headings

  • Neoplasms, Experimental
  • Monocytes
  • Mice, Knockout
  • Mice
  • Immunotherapy
  • Immunology
  • Immunity, Cellular
  • CD8-Positive T-Lymphocytes
  • Antigens, Neoplasm
  • Animals