Sustained regression of a primary choroidal melanoma under the influence of a therapeutic melanoma vaccine.

Mitchell, Malcolm S.; Liggett, Peter E.; Green, R L; Kan‐Mitchell, June; Murphree, A. Linn; Dean, Grace E.; Spears, Lucy; Walonker, Frances

doi:10.1200/jco.1994.12.2.396

Cited by 12 publications

(3 citation statements)

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“…Trials, usually consisting of a small number of patients, have investigated non‐specific tumour vaccines, using methanol‐extracted residue of bacilli Calmette‐Guérin3 and interferon 2α4, although tolerated by the patients, a substantial prognostic benefit was not observed. A case report of a successful response of a primary uveal melanoma to an active specific immunotherapy consisting of lysates of cutaneous melanoma cells underlined the need for more specific approaches5. Subsequent tumour vaccines based on tumour‐specific (such as MAGE‐1 and ‐3) and tumour‐differentiation antigens (such as gp100, tyrosinase, and Melan‐A) proved more effective than the above‐mentioned non‐specific tumour vaccines in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Expression of Fas and Fas ligand in uveal melanoma: biological implication and prognostic value

et al. 2001

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The interaction between Fas and Fas ligand is one possible immune escape mechanism used by tumour cells. In the present study, melanoma tissue from 103 patients who underwent enucleation for malignant uveal melanoma (iris melanomas excluded) was stained by immunohistochemistry with monoclonal antibodies specific for Fas, Fas ligand, CD3, CD8, and CD68. Histological and clinical data for these tumours were assessed. Both Fas and Fas ligand were detected in uveal melanomas. Cells of the monocyte/macrophage lineage rather than T-cells were the predominant group of tumour-infiltrating cells. The metastasis-free 5-year survival rates in the univariate analyses were considerably lower in patients with tumours that lacked Fas ligand expression (< 35% of the tumour cells), in the presence of more than 50 CD8-positive cells in 20 high-power fields and in the presence of more than 100 CD3-positive cells in 20 high-power fields. Fas and Fas ligand expression was associated with scleral infiltration. After adjustment for scleral infiltration, the predictive value of both Fas and Fas ligand expression was markedly decreased. In addition, the CD3- and CD8-positive cell count was positively associated with the histological cell type. Cox proportional hazards models showed that the presence of CD3- and CD8-positive cells was not an independent prognostic factor after adjusting for histological cell type. This preliminary observation deserves further investigation, which may shed more light on the immune escape mechanisms of this tumour and thus enable novel therapeutic strategies. The clinical relevance of this observation is limited, as more predictive parameters have been described for uveal melanoma.

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Section: Introductionmentioning

confidence: 99%

Expression of Fas and Fas ligand in uveal melanoma: biological implication and prognostic value

et al. 2001

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“…Other studies utilizing the Melacine vaccine, comprising 2 allogenic cell line lysates combined with the adjuvant DETOX (detoxified Freund's adjuvant), demonstrated similar yet somewhat more promising results 65,74. In Southwest Oncology Group's phase III randomized observation‐controlled Melacine trial of stage IIa melanoma, there was no significant benefit in RFS compared with the observation arm (hazard ratio: 0.92, P = 0.51) 75.…”

Section: Melanoma Vaccinesmentioning

confidence: 98%

Melanoma Immunotherapy

Sivendran

Glodny

Pan

et al. 2010

Mount Sinai J Medicine

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Melanoma immunotherapy has been an area of intense research for decades, and this work is now yielding more tangible results for patients. Work has focused on 4 main areas: cytokine therapy, administration of immune-modulating antibodies, adoptive T-cell therapy, and vaccines. Cytokine therapy is an established treatment for advanced melanoma, and immune-modulating antibodies have recently emerged as an exciting new area of drug development with efficacy now established in a phase III trial. Adoptive T-cell therapy provides the proof of principle that T cells can attack and eliminate tumors. It has been challenging, however, to adapt this treatment for widespread use. Vaccines have generally yielded poor results, but intratumor pathogen-based strategies have shown encouraging results in recent trials, perhaps due to stronger immune stimulation. A review of the field of melanoma immunotherapy is provided here, with emphasis on those agents that have reached clinical testing. Novel strategies to induce the immune system to attack melanomas are reviewed. In the future, it is envisioned that immunotherapy will have further application in combination with cytotoxic and targeted therapies.

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“…It is challenged for the predominantly immunosuppressive phenotype of tumor cells. Mitchell et al [40] reported regression of a large primary choroidal melanoma after treatment with a whole cell-based vaccine. The vaccine, called Melacine, consisted of lysates of two human cutaneous melanoma cell lines administered with immunologic adjuvant Detox.…”

Section: Whole Cell-based Vaccinesmentioning

confidence: 99%

Immunotherapy of Uveal Melanoma

Bosch

2011

Current Concepts in Uveal Melanoma

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Uveal melanoma is a malignancy with exceptional features for treatment with immunotherapy. Primary uveal melanoma can be treated with a variety of therapies that may limit the growth of the primary tumor in the eye and partially preserve vision. However, none of these treatment modalities prevents the development of metastases, which predominantly arise in the liver and universally remain fatal. Novel therapies are being explored for their effectiveness against uveal melanoma metastases and immunotherapy may be a potential option as an alternative or adjunctive treatment, even in the prophylactic setting. Uveal melanoma may be particularly responsive to T-cell-based immunotherapy because it originates in the immune-privileged eye. The localization of the primary tumor in the immune-privileged eye excuses the tumor cells from continuous immunological pressure. This may render primary uveal melanoma more immunogenic than tumor cells from non-privileged sites and allow expression of novel tumor antigens to which the patient's endogenous T cell repertoire is not tolerized. The clinical and genetic differences between cutaneous and uveal melanomas underscore the need for immunotherapy specifically designed for uveal melanoma patients. In this review, the current developments in the field of immunotherapy for uveal melanoma are discussed, with a special emphasis on T-cell-based strategies.

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Sustained regression of a primary choroidal melanoma under the influence of a therapeutic melanoma vaccine.

Cited by 12 publications

References 12 publications

Expression of Fas and Fas ligand in uveal melanoma: biological implication and prognostic value

Expression of Fas and Fas ligand in uveal melanoma: biological implication and prognostic value

Melanoma Immunotherapy

Immunotherapy of Uveal Melanoma

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