Tumor regression responses in melanoma patients treated with a peptide encoded by gene <i>MAGES‐3</i>

Marchand, Marie; Weynants, P.; Rankin, Elaine M.; Arienti, Flavio; Belli, Filiberto; Parmiani, Giorgio; Cascinelli, Natale; Bourlond, A; Vanwijck, Romain; Humblet, Yves

doi:10.1002/ijc.2910630622

Cited by 374 publications

(162 citation statements)

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“…1,2 A number of them are presently being evaluated in clinical immunization trials. [3][4][5][6][7] In this study, we applied TMA technology to the analysis of MAGE-A4 expression in bladder cancers. Our results show that this TAA is expressed in tumors of different histologic types and most frequently in squamous cell carcinomas.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 Capitalizing on this background, clinical immunization trials are currently being implemented, showing promising preliminary results. [3][4][5][6][7] Concomitantly, the potential relevance of these proteins as tumor markers is also emerging. Clinical studies suggest that MAGE TAA expression is prevailingly detectable in highly aggressive, poorly differentiated tumors, 8 -10 thereby increasing their interest as therapeutic targets.…”

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confidence: 99%

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Prognostic relevance of MAGE‐A4 tumor antigen expression in transitional cell carcinoma of the urinary bladder: A tissue microarray study

Köcher

Zheng

Bolli

et al. 2002

Intl Journal of Cancer

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TAAs of the MAGE family are mostly studied as targets of specific immune responses. Their potential relevance as tumor markers has also been underlined. We used a MAb, 57B, recognizing MAGE-A4 protein in paraffin-embedded sections, to evaluate its expression in bladder cancers by employing TMA including 2,317 samples from 1,849 patients. In 2,090/2,317 cases (90.2%), immunostaining yielded interpretable results. Since for some patients more than 1 sample was available, only interpretable first biopsies (n ‫؍‬ 1,628) were considered. MAGE-A4 protein was expressed at significantly (p < 0.001) higher frequency in squamous (25/55, 45.5%) than in adeno (4/15, 26.7%), sarcomatoid (4/14, 28.6%), small cell (5/20, 25%) or transitional cell (281/1,522, 18.5%) carcinomas. In TCCs, overall MAGE-A4 positivity was significantly correlated with invasive phenotype (p < 0.001) and high tumor grade (p < 0.0001). Clinical data from 908 TCC patients were retrospectively evaluated, revealing that strong 57B staining was highly significantly associated with decreased tumorspecific survival (p < 0.0001). These data suggest that evaluation of MAGE-A4 protein expression is useful in the identification of groups of TCCs characterized by severe prognosis, thus possibly providing indications for early MAGE TAA-targeted immunotherapy. © 2002 Wiley-Liss, Inc. Key words: bladder cancer; 57B MAb; MAGE-A4; tissue microarray; tumor-specific survivalHuman TAAs of the MAGE family are recognized by CTLs from tumor patients. 1,2 Capitalizing on this background, clinical immunization trials are currently being implemented, showing promising preliminary results. [3][4][5][6][7] Concomitantly, the potential relevance of these proteins as tumor markers is also emerging. Clinical studies suggest that MAGE TAA expression is prevailingly detectable in highly aggressive, poorly differentiated tumors, 8 -10 thereby increasing their interest as therapeutic targets.In particular, MAGE gene expression has also been described in urinary bladder cancers, 8 but the number of cases was too low to allow evaluation of clinicopathologic or prognostic correlations.TMA technology offers the unique possibility to rapidly analyze large numbers of tumors. 11 Minute tissue cylinders (diameter 0.6 mm) are taken from hundreds of different primary tumor blocks and subsequently brought into 1 empty recipient paraffin block. Sections from such array blocks can then be used for simultaneous in situ analysis of hundreds or thousands of tumors at the DNA, RNA or protein level.In this study, we used a bladder cancer TMA containing 2,317 specimens to evaluate the frequency of MAGE-A4 protein expression as detected by a specific MAb (57B) and to assess its correlation with tumor phenotype and clinical outcome. MATERIAL AND METHODS MAb 57BReagent 57B was generated by our group using as immunogen recombinant MAGE-A3 protein. 12 Immunohistochemic studies carried out in different laboratories have emphasized that, although 57B identifies multiple MAGE gene products in transfected cells, ...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Prognostic relevance of MAGE‐A4 tumor antigen expression in transitional cell carcinoma of the urinary bladder: A tissue microarray study

Köcher

Zheng

Bolli

et al. 2002

Intl Journal of Cancer

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“…3,4 To date, most melanoma vaccines have made use of defined melanoma antigens like MAGE-1 and -3, MART-1/Melan A and gp100. [5][6][7][8][9] Although promising responses have been obtained, the defined melanoma antigens are not essential for tumor survival, and genetic alterations may lead to tumor escape. The use of peptide cocktails or allogenic tumor cell lines as source of antigen may initiate broader immune responses.…”

Section: Introductionmentioning

confidence: 99%

Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA

et al. 2006

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We have developed an individualized melanoma vaccine based on transfection of autologous dendritic cells (DCs) with autologous tumor-mRNA. Dendritic cells loaded with complete tumor-mRNA may generate an immune response against a broad repertoire of antigens, including unique patient-specific antigens. The purpose of the present phase I/II trial was to evaluate the feasibility and safety of the vaccine, and the ability of the DCs to elicit T-cell responses in melanoma patients. Further, we compared intradermal (i.d.) and intranodal (i.n.) vaccine administration. Twenty-two patients with advanced malignant melanoma were included, each receiving four weekly vaccines. Monocyte-derived DCs were transfected with tumor-mRNA by electroporation, matured and cryopreserved. We obtained successful vaccine production for all patients elected. No serious adverse effects were observed. A vaccine-specific immune response was demonstrated in 9/19 patients evaluable by T-cell assays (T-cell proliferation/interferon-g ELISPOT) and in 8/18 patients evaluable by delayed-type hypersensitivity (DTH) reaction. The response was demonstrated in 7/10 patients vaccinated intradermally and in 3/12 patients vaccinated intranodally. We conclude that immuno-gene-therapy with the described DC-vaccine is feasible and safe, and that the vaccine can elicit in vivo T-cell responses against antigens encoded by the transfected tumor-mRNA. The response rates do not suggest an advantage in applying i.n. vaccination. Cancer Gene Therapy (2006) 13, 905-918.

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“…Some of these antigens are expressed in various tumours of different histological origins, but not in normal tissues other than testis. Therefore, these antigens have been designated cancer-testis antigens (CTAs) and their characteristics make them promising candidates for cancer-specific immunotherapy; clinical trials using peptides such as MAGE-1 or MAGE-3 are in progress for malignant melanoma (Mukherji et al, 1995;Marchand et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Expression of multiple cancer-testis antigen genes in gastrointestinal and breast carcinomas

et al. 2001

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Summary Cancer-testis antigens (CTAs) such as MAGE are selectively expressed in various types of human neoplasms but not in normal tissues other than testis. This characteristic feature of CTAs makes them promising antigens for cancer-specific immunotherapy. A critical requirement for this therapy is identification of promising antigens. In this study, we investigated the expression of 6 genes recently identified by serological analysis of antigens by recombinant expression (SEREX) libraries: NY-ESO-1, LAGE-1, SCP-1, SSX-1, SSX-2, and SSX-4, in many surgical samples of gastrointestinal and breast carcinomas using reverse transcription-polymerase chain reaction. We found relatively high expression of SCP-1 (23.5%) and SSX-4 (20.6%) in gastric carcinoma, LAGE-1 (39.1%) and NY-ESO-1 (23.9%) in oesophageal carcinoma, and SCP-1 (34.1%) in breast carcinoma. We also found frequent synchronous expression with MAGE, including LAGE-1 (46.2%) in oesophageal carcinoma, SSX-4 (46.7%) in gastric carcinoma, and SCP-1 (38.3%) in breast carcinoma. Immunohistochemical analysis of the tumour samples expressing both MAGE-4 and NY-ESO-1 genes demonstrated differences in distribution between MAGE-4 and NY-ESO-1 in serial sections. We concluded that NY-ESO-1, LAGE-1, SCP-1 and SSX-4 genes may be promising candidates for cancer-specific immunotherapy in addition to MAGE, and that polyvalent cancer vaccines may be useful in cases of heterogeneous expressions of CTA genes in gastrointestinal and breast carcinomas.

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Tumor regression responses in melanoma patients treated with a peptide encoded by gene MAGES‐3

Cited by 374 publications

References 6 publications

Prognostic relevance of MAGE‐A4 tumor antigen expression in transitional cell carcinoma of the urinary bladder: A tissue microarray study

Prognostic relevance of MAGE‐A4 tumor antigen expression in transitional cell carcinoma of the urinary bladder: A tissue microarray study

Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA

Expression of multiple cancer-testis antigen genes in gastrointestinal and breast carcinomas

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