Flt3-ligand induces transient tumor regression in an ectopic treatment model of major histocompatibility complex-negative prostate cancer
| Autor: | R P, Ciavarra, K D, Somers, R R, Brown, W F, Glass, P J, Consolvo, G L, Wright, P F, Schellhammer |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Histocompatibility Antigens Class I Remission Induction Dose-Response Relationship Immunologic Membrane Proteins Prostatic Neoplasms Mice Transgenic Macrophage Activation Immunohistochemistry Monocytes Rats Mice Inbred C57BL Interferon-gamma Mice Disease Progression Tumor Cells Cultured Animals Immunotherapy Neoplasm Recurrence Local Cell Division Neoplasm Transplantation |
| Zdroj: | Cancer research. 60(8) |
| ISSN: | 0008-5472 |
| Popis: | We assessed the in vivo efficacy of Flt3-ligand (Flt3-L) treatment in C57BL/6 mice bearing a well-established MHC class I-negative prostate carcinoma TRAMP-C1. Flt3-L immunotherapy was initiated approximately 30 days after tumor inoculation, a time whenor =80% of the mice had palpable TRAMP-C1 tumors. Treatment with Flt3-L at 10 microg/day for 21 consecutive days suppressed TRAMP-C1 tumor growth and induced tumor stabilization (P = 0.0337). Enhanced tumor regression was demonstrated at a higher dose of 30 microg/day (P0.0001). Tumors excised from mice treated with Flt3-L were smaller than carrier-treated controls and contained a more pronounced mixed inflammatory cell infiltrate primarily composed of mphi. In regressor nice, tumors reappeared at the site of injection when Flt3-L therapy was terminated. When the experiment was repeated with MHC class I-positive TRAMP-C1 cells, tumor stabilization and/or regression was again observed after treatment (P0.0001); however, once again, tumors reappeared after the termination of therapy despite an extended treatment schedule (35 days). MHC class I-negative variants were present in tumors isolated from carrier- and Flt3-L-treated mice, and this phenotype could be reversed by IFN-gamma treatment in vitro. Thus, Flt3-L treatment of mice with preexisting transplantable prostate tumors results in tumor regression that is dose-dependent and accompanied by a pronounced mixed-cell inflammatory tumor infiltrate. However, disease relapse was invariably observed after the termination of therapy, which suggests that Flt3-L treatment of advanced MHC- prostate cancers will require adjuvant modalities to achieve a durable response. |
| Databáze: | OpenAIRE |
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