Elsevier

Cellular Immunology

Volume 179, Issue 1, 10 July 1997, Pages 84-95
Cellular Immunology

Regular Article
Immunotherapeutic Potential of Tumor Antigen-Pulsed and Unpulsed Dendritic Cells Generated from Murine Bone Marrow☆,☆☆

https://doi.org/10.1006/cimm.1997.1151Get rights and content

Abstract

Dendritic cells (DC) are highly efficient antigen-presenting cells able to capture, process, and present antigens to naive and primed T-cells. In this study, we have investigated the ability of DC, derived from murine bone marrow and pulsed with tumor cell extracts, to induce regression of preexisting tumors. In an experimental model of B16 melanoma in B6 mice, a significant reduction in metastatic nodules in the lungs was observed in tumor-bearing animals treated with either DC alone or DC pulsed with tumor extracts. Kinetic studies demonstrate that the efficacy of these tumor vaccines is inversely related to tumor burden. In this model, tumor-specific cytotoxic T-cells (CTL) could also be inducedin vitrofrom spleen cells derived from tumor-bearing animals treated with DC pulsed with tumor extracts. Untreated mice had no CTL. Furthermore, DC alone elicited tumor-specific CTL responses in tumor-bearing mice, but not in naive mice. Immune cell depletion experiments show that the therapeutic effects of DC are primarily mediated by CD8+T-cells, while CD4+T-cells and NK cells are involved in DC-mediated antitumor immunity to a limited extent. These results illustrate the potential use of DC and DC pulsed with tumor extracts as potent therapeutic reagents for cancer and provide a rationale for using DCin vivoto eliminate disseminated tumors or residual tumor deposits following surgery.

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    • Cited by (0)

    ☆

    This work was supported in part by NIH Grant RO1-CA64949 (T.L.D.), RO1-CA64959 (H.F.S.), and VA Grant Seigler0001.

    ☆☆

    Abbreviations used: APC, antigen-presenting cellscpm, counts per minute; CTL, cytotoxic T-cells; DC, dendritic cells; DB, dendritic cells pulsed with B16 tumor cell extracts; FBS, fetal bovine serum; HBSS, Hanks' balanced salt solution; HEL, hen egg lysozyme; ip, intraperitoneally; iv, intravenously; MLR, mixed lymphocyte reaction; MLTR, mixed lymphocyte and tumor reaction; SUPER, 48-hr culture supernatants from L929 mouse fibroblasts; TAA, tumor-associated antigens;

    2

    To whom reprint requests should be addressed.

    3

    Members of Duke Comprehensive Cancer Center.

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