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[The effect of immunotherapy and hyperthermia on advanced or recurrent ovarian and uterine cancer - 229 clinical cases].
Okt. 2014 | Nakamura, Kana; Hanazawa, Sayaka; Takeda, Takashi; Sumiyoshi, Rumi; Kobayashi, Shogo; Takeda, Hiroko; Takeda, Tsutomu
We treated 116 advanced or recurrent ovarian cancer and 102 uterine cancer patients with hyperthermia and/or immunotherapy(2005/7-2013/11). Of these, 63, 31, and 8 patients had cervical cancer, endometrial cancer, and uterine sarcoma, respectively. Standard therapy showed no effect or was refused by these patients. Twenty-nine(25.0%)ovarian cancer patients experienced a clinical benefit(complete response[CR], partial response[PR], and long-term stable disease[SD], >6 months). The effective rate of a combination of therapies including activated lymphocyte therapy, dendritic cell therapy, and hyperthermia was 47.5%. Thirteen(12.7%)uterine cancer patients experienced a clinical benefit. The effective rates for cervical cancer, endometrial cancer, and uterine sarcoma were 7.9%, 22.5%, and 12.5%, respectively. Both hyperthermia and immunotherapy were administered to successfully treat these patients. PMID 25335722

Vaccination with autologous tumour antigen-pulsed dendritic cells in advanced gynaecological malignancies: clinical and immunological evaluation of a phase I trial.
März 2002 | Hernando, Juan José; Park, Tjoung-Won; Kübler, Kirsten; Offergeld, Ruth; Schlebusch, Harald; Bauknecht, Thomas
Dendritic cell (DC)-based therapy has proven to be effective in patients with malignant lymphoma, melanoma, and renal and prostate carcinoma. In this phase I clinical trial, we have shown that patients with advanced gynaecological malignancies can be effectively vaccinated with DC pulsed with keyhole limpet haemocyanin (KLH) and autologous tumour antigens. Two patients with uterine sarcoma and six subjects with ovarian carcinoma received three to 23 intracutaneous injections of antigen-pulsed DC at 10-day or 4-week intervals. Three patients showed stable disease lasting 25 to 45 weeks, and five experienced tumour progression within the first 14 weeks. KLH- and tumour lysate-specific delayed-type hypersensitivity (DTH) reactions were observed in six and one patient, respectively. Lymphoproliferative responses to KLH and to tumour lysate stimulation were recorded in six patients and in two patients respectively. Tumour antigen-stimulated interferon-gamma (IFN-gamma) secretion by peripheral blood mononuclear cells (PBMC) in one patient was consistent with a T(H) type 1 cytokine bias. The treatment was safe, well tolerated, immunologically active and except for local cutaneous hypersensitivity devoid of significant adverse effects. PMID 11845259

Induction of tumour-specific CD8(+) cytotoxic T lymphocytes by tumour lysate-pulsed autologous dendritic cells in patients with uterine serous papillary cancer.
Feb. 2002 | Santin, A D; Bellone, S; Ravaggi, A; Roman, J J; Pecorelli, S; Parham, G P; Cannon, M J
Uterine serous papillary carcinoma is a highly aggressive variant of endometrial cancer histologically similar to high grade ovarian cancer. Unlike ovarian cancer, however, it is a chemoresistant disease from onset, with responses to combined cisplatinum-based chemotherapy in the order of 20% and an extremely poor prognosis. In this study, we demonstrate that tumour lysate-pulsed autologous dendritic cells can elicit a specific CD8(+) cytotoxic T lymphocyte response against autologous tumour target cells in three patients with uterine serous papillary cancer. CTL from patients 1 and 2 expressed strong cytolytic activity against autologous tumour cells, did not lyse autologous lymphoblasts or autologous EBV-transformed cell lines, and were variably cytotoxic against the NK-sensitive cell line K-562. Patient 3 CD8(+) T cells expressed a modest but reproducible cytotoxicity against autologous tumour cells only at the time of the first priming. Further priming attempts with PBL collected from patient 3 after tumour progression in the lumboaortic lymph nodes were unsuccessful. Cytotoxicity against autologous tumour cells could be significantly inhibited by anti-HLA class I (W6/32) and anti-LFA-1 MAbs. Highly cytotoxic CD8(+) T cells from patients 1 and 2 showed a heterogeneous CD56 expression while CD56 was not expressed by non-cytotoxic CD8(+) T cells from patient 3. Using two colour flow cytometric analysis of intracellular cytokine expression at the single cell level, a striking dominance of IFN-gamma expressors was detectable in CTL populations of patients 1 and 2 while in patient 3 a dominant population of CD8(+) T cells expressing IL-4 and IL-10 was consistently detected. Taken together, these data demonstrate that tumour lysate-pulsed DC can be an effective tool in inducing uterine serous papillary cancer-specific CD8(+) CTL able to kill autologous tumour cells in vitro. However, high levels of tumour specific tolerance in some patients may impose a significant barrier to therapeutic vaccination. These results may have important implications for the treatment in the adjuvant setting of uterine serous papillary cancer patients with active or adoptive immunotherapy. PMID 11857027