This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Radhakrishnan, S. Articles by Pease, L. R. Search for Related Content PubMed PubMed Citation Articles by Radhakrishnan, S. Articles by Pease, L. R.

Immunotherapeutic Potential of B7-DC (PD-L2) Cross-Linking Antibody In Conferring Antitumor Immunity

Departments of ¹ Immunology and ² Neurology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota

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.

This article has been cited by other articles:

				M. Rodriguez, A. E. Warrington, and L. R. Pease Invited Article: Human natural autoantibodies in the treatment of neurologic disease Neurology, April 7, 2009; 72(14): 1269 - 1276. [Abstract] [Full Text] [PDF]

				K. D. Pavelko, M. J. Hansen, and L. R. Pease CTL Activation Using the Natural Low-Affinity Epitope 222-229 from Tyrosinase-Related Protein 1 Leads to Tumor Rejection Cancer Res., April 1, 2009; 69(7): 3114 - 3120. [Abstract] [Full Text] [PDF]

				S. Radhakrishnan, L. N. Arneson, J. L. Upshaw, C. L. Howe, S. J. Felts, M. Colonna, P. J. Leibson, M. Rodriguez, and L. R. Pease TREM-2 Mediated Signaling Induces Antigen Uptake and Retention in Mature Myeloid Dendritic Cells J. Immunol., December 1, 2008; 181(11): 7863 - 7872. [Abstract] [Full Text] [PDF]

				S. Radhakrishnan, R. Cabrera, E. L. Schenk, P. Nava-Parada, M. P. Bell, V. P. Van Keulen, R. J. Marler, S. J. Felts, and L. R. Pease Reprogrammed FoxP3+ T Regulatory Cells Become IL-17+ Antigen-Specific Autoimmune Effectors In Vitro and In Vivo J. Immunol., September 1, 2008; 181(5): 3137 - 3147. [Abstract] [Full Text] [PDF]

				K. D. Pavelko, K. L. Heckman, M. J. Hansen, and L. R. Pease An Effective Vaccine Strategy Protective against Antigenically Distinct Tumor Variants Cancer Res., April 1, 2008; 68(7): 2471 - 2478. [Abstract] [Full Text] [PDF]

				S. Radhakrishnan, L. T. Nguyen, B. Ciric, V. P. Van Keulen, and L. R. Pease B7-DC/PD-L2 Cross-Linking Induces NF-{kappa}B-Dependent Protection of Dendritic Cells from Cell Death J. Immunol., February 1, 2007; 178(3): 1426 - 1432. [Abstract] [Full Text] [PDF]

				R. S. Kornbluth and G. W. Stone Immunostimulatory combinations: designing the next generation of vaccine adjuvants J. Leukoc. Biol., November 1, 2006; 80(5): 1084 - 1102. [Abstract] [Full Text] [PDF]

				F. A. Blocki, S. Radhakrishnan, V. P. Van Keulen, K. L. Heckman, B. Ciric, C. L. Howe, M. Rodriguez, E. Kwon, and L. R. Pease Induction of a gene expression program in dendritic cells with a cross-linking IgM antibody to the co-stimulatory molecule B7-DC FASEB J, November 1, 2006; 20(13): 2408 - 2410. [Abstract] [Full Text] [PDF]

				Y. Zhang, Y. Chung, C. Bishop, B. Daugherty, H. Chute, P. Holst, C. Kurahara, F. Lott, N. Sun, A. A. Welcher, et al. Regulation of T cell activation and tolerance by PDL2 PNAS, August 1, 2006; 103(31): 11695 - 11700. [Abstract] [Full Text] [PDF]

				G. Lizee, L. G. Radvanyi, W. W. Overwijk, and P. Hwu Immunosuppression in melanoma immunotherapy: potential opportunities for intervention. Clin. Cancer Res., April 1, 2006; 12(7): 2359s - 2365s. [Abstract] [Full Text] [PDF]

				S. Radhakrishnan, E. Celis, and L. R. Pease B7-DC cross-linking restores antigen uptake and augments antigen-presenting cell function by matured dendritic cells PNAS, August 9, 2005; 102(32): 11438 - 11443. [Abstract] [Full Text] [PDF]

				J. Bayry, S. Lacroix-Desmazes, M. D. Kazatchkine, O. Hermine, D. F. Tough, and S. V. Kaveri Modulation of Dendritic Cell Maturation and Function by B Lymphocytes J. Immunol., July 1, 2005; 175(1): 15 - 20. [Abstract] [Full Text] [PDF]

				Y. Ohigashi, M. Sho, Y. Yamada, Y. Tsurui, K. Hamada, N. Ikeda, T. Mizuno, R. Yoriki, H. Kashizuka, K. Yane, et al. Clinical Significance of Programmed Death-1 Ligand-1 and Programmed Death-1 Ligand-2 Expression in Human Esophageal Cancer Clin. Cancer Res., April 15, 2005; 11(8): 2947 - 2953. [Abstract] [Full Text] [PDF]