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Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice.

Publication ,  Journal Article
McNamara, JO; Kolonias, D; Pastor, F; Mittler, RS; Chen, L; Giangrande, PH; Sullenger, B; Gilboa, E
Published in: J Clin Invest
January 2008

4-1BB is a major costimulatory receptor that promotes the survival and expansion of activated T cells. Administration of agonistic anti-4-1BB Abs has been previously shown to enhance tumor immunity in mice. Abs are cell-based products posing significant cost, manufacturing, and regulatory challenges. Aptamers are oligonucleotide-based ligands that exhibit specificity and avidity comparable to, or exceeding, that of Abs. To date, various aptamers have been shown to inhibit the function of their cognate target. Here, we have described the development of an aptamer that binds 4-1BB expressed on the surface of activated mouse T cells and shown that multivalent configurations of the aptamer costimulated T cell activation in vitro and mediated tumor rejection in mice. Because aptamers can be chemically synthesized, manufacturing and the regulatory approval process should be substantially simpler and less costly than for Abs. Agonistic aptamers could therefore represent a superior alternative to Abs for the therapeutic manipulation of the immune system.

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

January 2008

Volume

118

Issue

1

Start / End Page

376 / 386

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Neoplasm Transplantation
  • Mice, Inbred DBA
  • Mice, Inbred BALB C
  • Mice
  • Mastocytoma
  • Lymphocyte Activation
  • Immunology
  • Humans
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
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McNamara, J. O., Kolonias, D., Pastor, F., Mittler, R. S., Chen, L., Giangrande, P. H., … Gilboa, E. (2008). Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice. J Clin Invest, 118(1), 376–386. https://doi.org/10.1172/JCI33365
McNamara, James O., Despina Kolonias, Fernando Pastor, Robert S. Mittler, Lieping Chen, Paloma H. Giangrande, Bruce Sullenger, and Eli Gilboa. “Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice.J Clin Invest 118, no. 1 (January 2008): 376–86. https://doi.org/10.1172/JCI33365.
McNamara JO, Kolonias D, Pastor F, Mittler RS, Chen L, Giangrande PH, et al. Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice. J Clin Invest. 2008 Jan;118(1):376–86.
McNamara, James O., et al. “Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice.J Clin Invest, vol. 118, no. 1, Jan. 2008, pp. 376–86. Pubmed, doi:10.1172/JCI33365.
McNamara JO, Kolonias D, Pastor F, Mittler RS, Chen L, Giangrande PH, Sullenger B, Gilboa E. Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice. J Clin Invest. 2008 Jan;118(1):376–386.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

January 2008

Volume

118

Issue

1

Start / End Page

376 / 386

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Neoplasm Transplantation
  • Mice, Inbred DBA
  • Mice, Inbred BALB C
  • Mice
  • Mastocytoma
  • Lymphocyte Activation
  • Immunology
  • Humans
  • Female