Immunoregulation of intraocular tumours

Niederkorn, Jérry Y.

doi:10.1038/eye.1997.60

Cited by 29 publications

(39 citation statements)

References 24 publications

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“…Together, these data indicate that immunization against melanoma Ag-derived peptides in the presence of P40 is efficient enough to prime CTL responses involved in tumor rejection both after tumor challenge and in a spontaneous tumor situation. This is remarkable, especially because the latter is an intraocular tumor, a type particularly resistant to immune-mediated rejection (36).…”

Section: Discussionmentioning

confidence: 99%

Cancer Vaccine Design: A Novel Bacterial Adjuvant for Peptide-Specific CTL Induction

Miconnet

Coste

Beermann

et al. 2001

The Journal of Immunology

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The recent identification of tumor Ags as potential vaccines has prompted the search for efficient adjuvants and delivery systems, especially in the case of peptide-based vaccination protocols. Here, we investigated the adjuvant potential of the recombinant 40-kDa outer membrane protein of Klebsellia pneumoniae (P40) for specific CTL induction. We studied the CTL response induced in HLA-A*0201/Kb transgenic mice immunized with peptides derived from two melanoma-associated differentiation Ags, the HLA-A*0201-restricted decapeptide Melan-A26–35 substituted at position 2 and the Kb-restricted tyrosinase-related protein 2181–188 T cell epitope. We found that both peptides are able to generate a specific CTL response when mixed with the protein in the absence of conventional adjuvant. This CTL response is a function of the amount of P40 used for immunization. Moreover, the CTL response generated against the tyrosinase-related protein 2181–188 peptide in presence of P40 is associated with tumor protection in two different experimental models and is independent of the presence of CD4+ T lymphocytes. Thus, the recombinant bacterial protein P40 functions as a potent immunological adjuvant for specific CTL induction.

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Section: Discussionmentioning

confidence: 99%

Cancer Vaccine Design: A Novel Bacterial Adjuvant for Peptide-Specific CTL Induction

Miconnet

Coste

Beermann

et al. 2001

The Journal of Immunology

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“…[26][27][28][29] The interior of the eye is endowed with multiple factors and regulatory mechanisms that might hinder immunotherapeutic agents, including the expression of complement regulatory proteins (CRP) on cell membranes of multiple cells in the eye and the presence of soluble forms of CRP in the ocular fluids. 27 Accordingly, experiments were conducted to determine whether UV3 affected the growth of uveal melanoma cells transplanted into the AC.…”

Section: Uv3 Has a Significant Effect On The Growth Of Intraocular Uvmentioning

confidence: 99%

Effect of an anti‐CD54 (ICAM‐1) monoclonal antibody (UV3) on the growth of human uveal melanoma cells transplanted heterotopically and orthotopically in SCID mice

Wang

Coleman

Pop

et al. 2005

Intl Journal of Cancer

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We have shown that administration of a novel anti-CD54 monoclonal antibody (UV3) results in long-term survival of SCID mice bearing human myeloma xenografts. Previous studies have demonstrated a link between the expression of CD54 and the progression of uveal melanoma. Our study assessed the expression of CD54 on 7 human uveal melanoma cell lines and 3 cell lines established from uveal melanoma metastases. In vivo studies examined the efficacy of systemic and local administration of UV3 antibody on the progression of uveal melanoma cells transplanted either heterotopically or orthotopically into SCID mice. Five of the 7 primary uveal melanoma cell lines and all 3 of the metastases cell lines expressed CD54. Intraperitoneal injection of either IgG or F(ab 0 ) 2 fragments of UV3 significantly inhibited the growth of subcutaneous and intraocular melanomas. Subconjunctival injection of either IgG or F(ab 0 ) 2 fragments of UV3 produced a significant reduction in the growth of intraocular melanomas, even if the antibody was administered after the appearance of intraocular tumors. The results indicate that both primary and metastatic human uveal melanoma cells express CD54. The marked inhibition of intraocular and subcutaneous uveal melanoma progression suggests that UV3 antibody is a promising therapeutic agent for further evaluation in patients with uveal melanoma. This is especially noteworthy, as no existing therapeutic modality prevents metastasis of uveal melanoma or prolongs the survival of patients with uveal melanoma. ' 2005 Wiley-Liss, Inc.Key words: anterior chamber; eye; CD54; immunotherapy; uveal melanoma Uveal melanoma is the most common intraocular malignancy in adults and occurs with a frequency of 6 to 7 cases per one million adults. 1 Although cutaneous and uveal melanomas share a neural crest origin, they differ significantly in their epidemiological, 2 cytogenetic 3 , metastatic 4-6 and immunological 4 characteristics. One of the remarkable differences between cutaneous and uveal melanomas is their metastatic behavior. Although skin melanomas metastasize to almost any organ, uveal melanoma displays a propensity to spread to the liver. Indeed, liver metastases are present in up to 95% of the patients who die from uveal melanomas. [7][8][9][10] Although there have been advances in the treatment of primary uveal melanomas, the 5-year survival rate for uveal melanoma patients has not improved in the past 30 years. 1,10 Moreover, no therapeutic modality prevents the metastasis of uveal melanoma or prolongs the survival of patients. 11 Studies have suggested a correlation between the expression of CD54 and the progression of skin and uveal melanomas. 12,13 Expression of CD54 was detected in 81-85% of human uveal melanoma specimens. 13,14 Reduced expression of CD54 in primary uveal melanomas has been associated with increased metastatic disease. 13 CD54 is an important ligand for leukocytes and is believed to be involved in immune surveillance. 15,16 Intravenous administration of MAb against human CD54 (U...

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“…What triggers the sudden enlargement of a uveal melanocytic lesion remains highly speculative. Uveal melanomas express melanoma-specific and melanoma-associated antigens that can elicit humoral and cellular immune responses (Niederkorn 1997). Effective tumor immunity is however, prevented in oculi by suppression of delayed type hypersensitivity and natural killer cells, anterior chamber-associated immune deviation and resistance to complement mediated lysis through membrane bound regulators CD55 or CD59 (Niederkorn 1997;Goslings et al 1996).…”

Section: Discussionmentioning

confidence: 99%

“…Uveal melanomas express melanoma-specific and melanoma-associated antigens that can elicit humoral and cellular immune responses (Niederkorn 1997). Effective tumor immunity is however, prevented in oculi by suppression of delayed type hypersensitivity and natural killer cells, anterior chamber-associated immune deviation and resistance to complement mediated lysis through membrane bound regulators CD55 or CD59 (Niederkorn 1997;Goslings et al 1996). Recently, decreased level of cycline-dependent kinases inhibitor p27 has been found to account for the uncontrolled proliferation of melanocytes (Mouriaux et al 1999).…”

Section: Discussionmentioning

confidence: 99%

Sequential development of bilateral primary choroidal melanoma

Kıratlı

Bilgiç

2000

Acta Ophthalmologica Scandinavica

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ABSTRACT.Purpose: A case of a woman who had bilateral choroidal melanoma diagnosed sequentially 20 months apart and managed conservatively is described. Methods: The first eye having a juxtapapillary melanoma was treated with a notched episcleral radioactive plaque. The second eye, initially containing a small nevus with unequivocal rapid growth, was managed with diode laser transpupillary thermotherapy. Results: Both tumors regressed considerably following treatment and the patient retained good visual acuity in both eyes. No other malignancies or metastasis were detected during the follow-up period. Conclusions: A small choroidal nevus rapidly grew after treating a choroidal melanoma in the fellow eye. Close follow-up of such patients is mandatory. Also, conservative treatment should be opted whenever possible given the unpredictable course of the opposite melanocytic lesion.

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Immunoregulation of intraocular tumours

Abstract: SUMMARY

Cited by 29 publications

References 24 publications

Cancer Vaccine Design: A Novel Bacterial Adjuvant for Peptide-Specific CTL Induction

Cancer Vaccine Design: A Novel Bacterial Adjuvant for Peptide-Specific CTL Induction

Effect of an anti‐CD54 (ICAM‐1) monoclonal antibody (UV3) on the growth of human uveal melanoma cells transplanted heterotopically and orthotopically in SCID mice

Sequential development of bilateral primary choroidal melanoma

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