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DC Therapy (dc + therapy)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

DC therapy induces long-term NK reactivity to tumors via host DC

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2009
Kanako Shimizu
Abstract We vaccinated mice with DC loaded with or without invariant NKT-cell ligand ,-galactosylceramide and evaluated long-term resistance against tumor challenge. When mice had been given either DC or DC/galactosylceramide and were challenged with tumor cells even 6,12 months later, both NK and NKT cells were quickly activated to express CD69 and produce IFN-,. The NK cells could resist a challenge with several different tumors in vivo. The activated NK and NKT cells could be depleted with anti-NK1.1 treatment. In spite of this, the activated cells recovered, indicating that tumor-responsive NK and NKT cells were being generated continuously as a result of vaccination with DC and were not true memory cells. The NK and NKT antitumor response in DC-vaccinated mice depended on CD4+ T cells, but neither CD8+T cells nor CD4+CD25+ regulatory T cells. However, both vaccine DC and host DC were required for the development of long-term, tumor reactive innate immunity. These results indicate that DC therapy in mice induces long-lasting innate NK- and NKT-cell activation through a pathway that requires host DC and CD4+ T cells and that the continued generation of active NK cells resists the establishment of metastases in vivo. [source]

Immunotherapy against metastatic renal cell carcinoma with mature dendritic cells

INTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2007
Akihiko Matsumoto
Objective: We performed a clinical trial of immunotherapy using autologous mature dendritic cells (DC) pulsed with autologous tumor lysate, for patients with metastatic renal cell carcinoma (RCC). Methods: Patients with refractory metastatic RCC were enrolled in the study. All of them received interferon (IFN)-, treatment after nephrectomy and were followed over 3 months prior to this study. Autologous monocyte-derived immature DC were pulsed with lysate from autologous primary tumor as the antigen and keyhole limpet hemocyanin (KLH) as immunomodulator, and cultured in the presence of tumor necrosis factor (TNF)-,, interleukin (IL)-1,, and prostaglandin (PG)E2 to generate mature DC. Mature DC were injected intradermally near bilateral inguinal lymph nodes of the patients. A delayed-type hypersensitivity (DTH) test and enzyme-linked immunospot (ELISPOT) assay were performed to evaluate the immunological response. After 4 months from first injection, the clinical effect was evaluated by diagnostic imaging. Results: The treatments were well tolerated without significant toxicity by the patients who were an average of 65.7 years old and had multiple metastases in the lung and other organs. One of the two patients developed a positive DTH reaction to tumor lysate and the other patient only to KLH. The patient with a positive DTH reaction to tumor lysate had stable disease in the clinical evaluation. Conclusions: We confirmed the safety of DC therapy in this clinical trial. The DTH test revealed that the DC therapy induced immunological response to RCC. On the other hand, it was necessary to reconsider the patient selection criteria. [source]

Phase I/II clinical trial of sequential subcutaneous and intravenous delivery of dendritic cell vaccination for refractory multiple myeloma using patient-specific tumour idiotype protein or idiotype (VDJ)-derived class I-restricted peptides

BRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2007
Antonio Curti
Summary Fifteen multiple myeloma (MM) patients who had failed maintenance therapy after tandem autologous stem cell transplantation underwent anti-idiotype (Id) vaccination with dendritic cells (DCs). CD14+ -derived DCs were loaded with the autologous Id as whole protein (=6) or Id-derived class I-restricted peptides (=9) and keyhole limpet hemocyanin (KLH). Vaccination consisted of three subcutaneous (sc) and two intravenous injections of increasing DC doses at 2 weeks interval. DC therapy was well tolerated. Most patients developed both humoral and T-cell responses to KLH, suggesting immunocompetence. Eight of 15 patients developed an Id-specific T-cell proliferative response, 8/15 increased interferon-,-secreting T cells and 4/15 showed an Id-positive delayed-type hypersensitivity test. Anti-Id cytotoxic T-lymphocyte precursors increased after DC vaccination in 2/2 evaluable patients. A more robust T-cell response was observed after sc DC injections and increased Id-specific T-cell proliferation was found up to 1 year after vaccination. VDJ-derived peptides were as effective as the whole protein in stimulating T-cell responses. Clinically, 7/15 patients have stable disease after a median follow-up of 26 months, one patient achieved durable partial remission after 40 months, and seven patients progressed. In conclusion, sc injections of cryopreserved Id-pulsed DCs were safe and, in contrast with intravenous administrations, induced anti-MM T-cell responses. [source]