A Randomized Trial of Adjuvant Chemotherapy and Immunotherapy in Cutaneous Melanoma.

Veronesi, Umberto; Adamus, J; Aubert, Carole E.; Bajetta, Emilio; Beretta, G; Bonadonna, Gianni; Bufalino, Rosaria; Cascinelli, Natale; Cocconi, Giorgio; Durand, Jean Bernard; DeMarsillac, J.; Ikonopisov, R. L.; Kiss, Béla; Lejeune, F.; MacKie, Rona M.; Madej, G; Mulder, Hillary; Mechl, Zdeněk; Milton, G. W.; Morabito, Alberto; Peter, Hans; Priario, Julio C; Paul, E.; Rümke, P; Sertoli, R.; Tomin, R

doi:10.1016/0002-9394(83)90368-9

Cited by 43 publications

(58 citation statements)

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“…Needless to say such information will greatly contribute to our understanding of the relationship between tumor and host and will open the way for a possible adoptive specific immunotherapy of this devastating desease, for which both chemotherapy and non-specific immunotherapy or a combination of the two, do not have significant effect (95).…”

Section: Discussionmentioning

confidence: 99%

Autologous cellular immune response to primary and metastatic human melanomas and its regulation by DR antigens expressed on tumor cells

et al. 1985

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Evidence for heterogeneity of several biological features of human malignant melanoma (Me) like morphology, cytogenetics, oncogenes activation, antigenic expression, metastatizing capacity and procoagulant activity are briefly reviewed in an attempt to distinguish findings related to primary vs. metastatic lesions. In our own studies monoclonal antibodies were used to study expression of MHC class I, class II products and of Me-associated antigens (MAA) on primary and metastatic Me cells. High expression of class I antigens was found in a high percentage of both primary and metastatic tumors, whereas DR and MAA showed a significant variation (from 3 to 90% of cells) in expression both in primary and in metastatic Me. When autologous cell-mediated immune responses were evaluated, it was found that Me cells from primary tumors but not those from lymph node metastases were able to stimulate autologous lymphocytes to proliferate and become cytotoxic for autologous Me. Clonal analysis of cytotoxic lymphocytes was then carried out in order to see whether the lack of lymphocytes reactivity to metastatic cells was due to the absence or to a low frequency of cytotoxic cells in the unstimulated PBL. CTL clones cytotoxic for autologous Me (Auto-Me) cells were indeed isolated. Three classes of CTL clones were identified: 1) one which is cytotoxic for Auto-Me; 2) a second one which lyse Auto-Me and allogeneic Me; and 3) a third one which is cytotoxic for Auto-Me and allogeneic normal and neoplastic cells. Metastatic Me cells, however, had the ability to suppress the stimulation of autologous PBL by alloantigens or IL-2. This effect was dose-dependent and was not due to absorption of IL-2 by Me cells. Since it has been reported that Me cells express class II MHC antigens, we investigated whether there was any correlation between autologous immune responses and DR expression on Me cells. Autologous lymphocytes stimulation was found to occur only with DR+ Me cells from primary lesions, whereas metastatic cells, either DR+ or DR-, did not stimulate autologous PBL. Moreover, the suppressive effect of metastatic Me cells was associated with their expression of DR antigens. The modulation of DR antigens on Me cells by Interferon-gamma correlated positively with their suppressive capacity. Thus, it appears that primary Me can behave differently from the metastatic one in their interactions with the immune system of autologous host. These findings suggest that DR antigens on Me cells may have an important role in the regulation of autologous immune responses.

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Section: Discussionmentioning

confidence: 99%

Autologous cellular immune response to primary and metastatic human melanomas and its regulation by DR antigens expressed on tumor cells

et al. 1985

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“…Die Gesamtüberlebens-zeit zeigte sich in keiner Studie signifikant verbessert [2,3,4]. In einer Studie führ-te eine adjuvante Chemotherapie sogar zu einer Verschlechterung der Prognose [13].…”

Section: Adjuvante Chemotherapieunclassified

Adjuvante systemische Therapie des Melanoms

Egberts²,

Hauschild³

et al. 2011

Hautarzt

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Despite intensive clinical and research efforts during the last decades the prognosis for patients with stage IV melanoma still remains fatal. An efficient adjuvant treatment for patients with a high risk of relapse and metastases is one of the most urgent fields in clinical research. Systemic adjuvant chemotherapy was not beneficial in terms of relapse-free or overall survival improvement in several clinical trials. Treatment with IFN-α-2a and -2b treatment was the first and as yet only adjuvant therapy which has been proven to show a benefit in controlled studies and to gain approval in Germany in the indications for adjuvant therapy. Current clinical research focuses on improved treatment schedules with conventional interferon compared to pegylated interferon and on the other hand on testing new compounds, such as the CTLA4 inhibitor ipilimumab or a vaccination against the MAGE-A3 peptide.

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Section: Adjuvante Chemotherapieunclassified

“…Die Gesamtüberlebenszeit zeigte sich in keiner Studie signifikant verbessert [2,3,4]. In einer Studie führte eine adjuvante Chemotherapie sogar zu einer Verschlechterung der Prognose [4]. Eine 3-armige Studie der Arbeitsgemeinschaft Dermatologische Onkologie (ADO) an 441 Patienten im resezierten Stadium III untersuchte die Wirksamkeit von Interferon α2a mit oder ohne DTIC im Vergleich zu alleiniger Beobachtung.…”

Section: Adjuvante Chemotherapieunclassified

“…Untersucht wurden z. B. Impfungen mit BCG (Bacille Calmette Guerin) oder Corynebacterium parvum sowie Misteltherapien (Iscador®; [4,6,7]). In der größten adjuvanten Therapiestudie zur BCG-Immunisierung zeigte sich weder für die mit BCG behandelten noch für die mit BCG in Kombination mit Dacarbazin behandelten Patienten ein Vorteil im Vergleich zu unbehandelten Kontrollen [4].…”

Section: Adjuvante Immuntherapieunclassified

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Aktuelle Aspekte der adjuvanten Therapie des malignen Melanoms

2010

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Despite intensive clinical and research efforts during recent decades, the prognosis of patients with stage IV melanoma still remains poor. Finding effective adjuvant treatment for patients with a high risk of relapse and metastasis is one of the most urgent needs in clinical research. Systemic adjuvant chemotherapy administered in several clinical trials offered no benefit in terms of improved relapse-free or overall survival. Interferon alpha-2a and -2b treatment was the first treatment in the adjuvant setting which has shown a treatment benefit and received approval in Germany. Today clinical research focuses on improved treatment schedules with conventional interferon compared to pegylated interferon as well as on new compounds such as CTLA4 inhibitors like ipilimumab or a vaccination against the MAGE-A3 peptide.

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A Randomized Trial of Adjuvant Chemotherapy and Immunotherapy in Cutaneous Melanoma.

Cited by 43 publications

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Autologous cellular immune response to primary and metastatic human melanomas and its regulation by DR antigens expressed on tumor cells

Autologous cellular immune response to primary and metastatic human melanomas and its regulation by DR antigens expressed on tumor cells

Adjuvante systemische Therapie des Melanoms

Aktuelle Aspekte der adjuvanten Therapie des malignen Melanoms

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