Immunotherapeutic potential of B7-DC (PD-L2) cross-linking antibody in conferring antitumor immunity

Suresh Radhakrishnan, Loc Tan Nguyen, Bogoljub Ciric, Dallas Flies, Virginia P. Van Keulen, Koji Tamada, Lieping Chen, Moses Rodriguez, Larry R. Pease

Research output: Contribution to journalArticle

Abstract

A naturally occurring human antibody potentiates dendritic cell function on cross-linking B7-DC (PD-L2), supporting robust T-cell responses in vitro. Moreover, treatment of dendritic cells with B7-DC cross-linking antibody resulted in secretion of interleukin-12, suggesting a TH1 polarization of this response. Here we show an in vivo immunotherapeutic effect of this B7-DC cross-linking antibody using a poorly immunogenic B16 melanoma tumor model. Treatment of mice systemically with antibody at the time of tumor cell engraftment prevented tumor growth in a CD4 and CD8 T-cell-dependent manner. The protective effect of B7-DC cross-linking antibody treatment was independent of endogenous antibody responses. Tumor-specific CTL precursors could be isolated from lymph nodes draining the tumor site in animals treated with B7-DC cross-linking antibody, but not from those treated with isotype control antibodies. The elicited antitumor responses in vivo were specific and long-lasting. More strikingly, treatment of mice with B7-DC cross-linking antibody after the tumors were established in the lungs resulted in protection in a CD8-, perforin-, and granzyme B-dependent fashion. Depletion of natural killer cells did not block the effects of treatment with B7-DC cross-linking antibody. Together, these findings demonstrate that cross-linking B7-DC with the human IgM antibody sHIgM12 can induce a protective immune response against a weakly antigenic experimental tumor and therefore has potential as a novel immunotherapeutic approach for treating cancer.

Original languageEnglish (US)
Pages (from-to)4965-4972
Number of pages8
JournalCancer Research
Volume64
Issue number14
DOIs
StatePublished - Jul 15 2004
Externally publishedYes

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Immunity
Antibodies
Neoplasms
Dendritic Cells
Neoplasm Antibodies
T-Lymphocytes
Experimental Melanomas
Interleukin-12
Natural Killer Cells
Antibody Formation
Immunoglobulin M
Lymph Nodes
Lung
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Radhakrishnan, S., Nguyen, L. T., Ciric, B., Flies, D., Van Keulen, V. P., Tamada, K., ... Pease, L. R. (2004). Immunotherapeutic potential of B7-DC (PD-L2) cross-linking antibody in conferring antitumor immunity. Cancer Research, 64(14), 4965-4972. https://doi.org/10.1158/0008-5472.CAN-03-3025

Immunotherapeutic potential of B7-DC (PD-L2) cross-linking antibody in conferring antitumor immunity. / Radhakrishnan, Suresh; Nguyen, Loc Tan; Ciric, Bogoljub; Flies, Dallas; Van Keulen, Virginia P.; Tamada, Koji; Chen, Lieping; Rodriguez, Moses; Pease, Larry R.

In: Cancer Research, Vol. 64, No. 14, 15.07.2004, p. 4965-4972.

Research output: Contribution to journalArticle

Radhakrishnan, S, Nguyen, LT, Ciric, B, Flies, D, Van Keulen, VP, Tamada, K, Chen, L, Rodriguez, M & Pease, LR 2004, 'Immunotherapeutic potential of B7-DC (PD-L2) cross-linking antibody in conferring antitumor immunity', Cancer Research, vol. 64, no. 14, pp. 4965-4972. https://doi.org/10.1158/0008-5472.CAN-03-3025
Radhakrishnan S, Nguyen LT, Ciric B, Flies D, Van Keulen VP, Tamada K et al. Immunotherapeutic potential of B7-DC (PD-L2) cross-linking antibody in conferring antitumor immunity. Cancer Research. 2004 Jul 15;64(14):4965-4972. https://doi.org/10.1158/0008-5472.CAN-03-3025
Radhakrishnan, Suresh ; Nguyen, Loc Tan ; Ciric, Bogoljub ; Flies, Dallas ; Van Keulen, Virginia P. ; Tamada, Koji ; Chen, Lieping ; Rodriguez, Moses ; Pease, Larry R. / Immunotherapeutic potential of B7-DC (PD-L2) cross-linking antibody in conferring antitumor immunity. In: Cancer Research. 2004 ; Vol. 64, No. 14. pp. 4965-4972.
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