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

53 Scopus citations

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Radhakrishnan, S., Nguyen, L. T., Ciric, B., Flies, D., Van Keulen, V. P., Tamada, K., Chen, L., Rodriguez, M., & 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