Tumor-associated embryonic antigen-expressing vaccines that target CCR6 elicit potent CD8+ T cell-mediated protective and therapeutic antitumor immunity.

Abstract

Despite its potency, the wider use of immunotherapy for B cell malignancies is hampered by the lack of well-defined tumor-specific Ags. In this study, we demonstrate that an evolutionarily conserved 37-kDa immature laminin receptor protein (OFA-iLRP), a nonimmunogenic embryonic Ag expressed by a variety of tumors, is rendered immunogenic if targeted to the APCs using the CCR6 ligands MIP3alpha/CCL20 and mDF2beta. The CCR6 targeting facilitated efficient Ag cross-presentation and induction of tumor-neutralizing CTLs. Although the Ag targeting alone, without activation of dendritic cells (DCs), is proposed to induce tolerance, and MIP3alpha does not directly activate DCs, the MIP3alpha-based vaccine efficiently induced protective and therapeutic antitumor responses. The responses were as strong as those elicited by the OFA-iLRP fusions with moieties that activated DCs and Th1-type cytokine responses, mDF2beta, or mycobacterial Hsp70 Ag. Although the same cDNA encodes the dimerized high-affinity mature 67-kDa mLRP that is expressed in normal tissues to stabilize the binding of laminin to cell surface integrins, the vaccines expressing OFA-iLRP elicited long-term protective CD8(+) T cell-mediated memory responses against syngeneic B cell lymphoma, indicating the potential application of these simple vaccines as preventive and therapeutic formulations for human use.

• Authors: Arya Biragyn, Roberta Schiavo, Purevdorj Olkhanud, Kenya Sumitomo, Alan King, Megan McCain, Fred E Indig, Giovanni Almanzar, Dolgor Baatar
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 179 Issue 2 Pg. 1381-8 (Jul 15 2007) ISSN: 0022-1767 [Print] United States
• PMID: 17617631 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Antigens, Neoplasm
• CCL20 protein, mouse
• CCR6 protein, mouse
• Cancer Vaccines
• Chemokine CCL20
• Chemokines, CC
• Macrophage Inflammatory Proteins
• Receptors, CCR6
• Receptors, Chemokine
• Receptors, Laminin
• oncofetal antigens

Topics

• Animals
• Antigen Presentation (immunology)
• Antigen-Presenting Cells (immunology)
• Antigens, Neoplasm (genetics, immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (immunology, therapeutic use)
• Chemokine CCL20
• Chemokines, CC (immunology)
• Cloning, Molecular
• Cytotoxicity, Immunologic
• Female
• Lymphoma, B-Cell (immunology, therapy)
• Macrophage Inflammatory Proteins (immunology)
• Mice
• Microscopy, Confocal
• Receptors, CCR6
• Receptors, Chemokine (immunology)
• Receptors, Laminin (genetics, immunology)
• Vaccination