The indolent course of cutaneous T-cell lymphoma (CTCL) patients makes them attractive candidates for immunotherapeutic strategies. However, tumor specific antigens are unknown in CTCL, and thus this is an obstacle to the development of CTCL vaccines. Recently, vaccinations with the tumor antigen repertoire has shown to be a superior strategy to elicit protective immunity for hematological malignancies since it does not require definition of tumor antigens or HLA haplotyping (

Borrello IM, Sotomayor EM. Cancer Control, 9:138–151,2002
). Studies have shown that dendritic cells (DC) transfected with tumor mRNA amplified from primary tumor cells can stimulate anti-tumor T cell responses (
Boczkowski et al, Cancer Research, 60: 1028–1034,2000
;
Muller et al, Blood, 103: 1763–1769, 2004
). In this study, we determined the efficacy of ex vivo induction of anti-CTCL T cell responses using autologous DCs transfected with tumor RNA amplified from CTCL cells. We established a protocol for amplification of whole CTCL mRNA. DCs were generated from CD14+monocytes of patients with CTCL, transfected with amplified tumor RNA (5μg/106), matured with IL-1β, TNF-α, IL-6, and PGE2, and co-cultured with autologous peripheral blood lymphocytes. Induction of CTCL-specific cytotoxic T lymphocytes (CTL), determined by IFN-γ and Granzyme B secretion, was measured by ELISPOT assays. As a result, DCs transfected with amplified tumor RNA induced a 1–3 fold increase in specific IFN-γ secreting and Granzyme B releasing CTLs, compared to control DCs that were not transfected, in 3 of 5 patients. There was only an induction of granzyme B releasing CTLs seen in the fourth patient. There was no induction of either IFN-γ secreting or granzyme B releasing CTLs in the fifth CTCL patient who had low CD8+ T cells in the peripheral blood. These data suggest that vaccinations using DCs transfected with amplified tumor RNA might be a potent new strategy in the treatment of CTCL. It provides the rationale for further investigation of a potentially clinically effective and broadly applicable treatment for CTCL patients, and has the advantage of not requiring large amounts of tumor cells or characterization of a specific relevant antigen in each patient.

Topics:
dendritic cells, lymphoma, t-cell, cutaneous, neoplasms, rna, t-lymphocytes, granzyme b, antigens, rna, messenger, tumor antigens, tumor cells

Disclosures: Reseach grant from Ladies Leukemia Leaque.

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2006, The American Society of Hematology
2006
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