Tumoral and Immunologic Response After Vaccination of Melanoma Patients With an ALVAC Virus Encoding MAGE Antigens Recognized by T Cells

Baren, Nicolas van; Bonnet, Marie-Laure; Dréno, Brigitte; Khammari, Amir; Dorval, Thierry; Piperno‐Neumann, Sophie; Líénard, Danielle; Speiser, Daniel E.; Marchand, Marie; Brichard, Vincent G.; Escudier, Bernard; Négrier, Sylvie; Dietrich, Pierre‐Yves; Maraninchi, D; Osanto, Susanne; Meyer, Ralf G.; Ritter, Gerd; Moingeon, Philippe; Tartaglia, Jim; Bruggen, Pierre van der; Coulie, Pierre G.; Boon, Thierry

doi:10.1200/jco.2005.08.375

Cited by 163 publications

(106 citation statements)

References 34 publications

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“…49 , 50 Moreover, treatment-driven TCR repertoire diversity has been related to different treatment vaccine formulations. 51 , 52 In melanoma, a highly restricted TCR repertoire has been linked to metastasis regression during cytokine therapy. 53 Neo-adjuvant Sipuleucel-T treatment of prostate cancer subjects has been shown to induce a narrowed TCR diversity in the periphery but enlarged in the tumor, with these differences reduced during the treatment, suggesting that vaccine-driven T cells were infiltrating the tumor.…”

Section: Discussionmentioning

confidence: 99%

Antigen-specificity and DTIC before peptide-vaccination differently shape immune-checkpoint expression pattern, anti-tumor functionality and TCR repertoire in melanoma patients

et al. 2018

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We have recently described that DNA-damage inducing drug DTIC, administered before peptide (Melan-A and gp100)-vaccination, improves anti-tumor CD8+ Melan-A-specific T-cell functionality, enlarges the Melan-A+ TCR repertoire and impacts the overall survival of melanoma patients. To identify whether the two Ags employed in the vaccination differently shape the anti-tumor response, herein we have carried out a detailed analysis of phenotype, anti-tumor functionality and TCR repertoire in treatment-driven gp100-specific CD8+ T cells, in the same patients previously analyzed for Melan-A. We found that T-cell clones isolated from patients treated with vaccination alone possessed an Early/intermediate differentiated phenotype, whereas T cells isolated after DTIC plus vaccination were late-differentiated. Sequencing analysis of the TCRBV chains of 29 treatment-driven gp100-specific CD8+ T-cell clones revealed an oligoclonal TCR repertoire irrespective of the treatment schedule. The high anti-tumor activity observed in T cells isolated after chemo-immunotherapy was associated with low PD-1 expression. Differently, T-cell clones isolated after peptide-vaccination alone expressed a high level of PD-1, along with LAG-3 and TIM-3, and were neither tumor-reactive nor polyfunctional. Blockade of PD-1 reversed gp100-specific CD8+ T-cell dysfunctionality, confirming the direct role of this co-inhibitory molecule in suppressing anti-tumor activity, differently from what we have previously observed for Melan-A+CD8+ T cells, expressing PD-1 but highly functional. These findings indicate that the functional advantage induced by combined chemo-immunotherapy is determined by the tumor antigen nature, T-cell immune-checkpoints phenotype, TCR repertoire diversity and anti-tumor T-cell quality and highlights the importance of integrating these parameters to develop effective immunotherapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Antigen-specificity and DTIC before peptide-vaccination differently shape immune-checkpoint expression pattern, anti-tumor functionality and TCR repertoire in melanoma patients

et al. 2018

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“…Clinical trials have shown that vaccination with MAGE has effect on metastases (Thurner et al, 1999;Marchand et al, 2003;Kruit et al, 2005;Lurquin et al, 2005;Van Baren et al, 2005), but improvement of MAGE vaccines is strongly needed. In previous studies, we have shown that immunisation with Mage-b combined with GM-CSF plasmid DNA and thioglycollate reduced the number of metastases by 65% compared with the control group in a highly metastatic breast tumour model, 4T1 (Gravekamp et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…The MAGE antigens are particularly interesting for the development of breast cancer vaccines, because their expression (MAGE-A and/or MAGE-B) has been frequently detected in human breast tumour biopsies (92%) (Park et al, 2002), but not in normal tissues (De Backer et al, 1995;De Plaen et al, 1999). Various clinical trials have shown that vaccination with MAGE-1 and -3 peptides or protein, in patients with melanoma was effective against metastases (Thurner et al, 1999;Marchand et al, 2003;Kruit et al, 2005;Lurquin et al, 2005;Van Baren et al, 2005). These human clinical trials not only show the potential of MAGE vaccination against metastases but also the need to further optimise the efficacy of MAGE-based vaccines to improve the clinical outcome.…”

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confidence: 99%

Mage-b vaccine delivered by recombinant Listeria monocytogenes is highly effective against breast cancer metastases

et al. 2008

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New therapies are needed that target breast cancer metastases. In previous studies, we have shown that vaccination with pcDNA3.1-Mage-b DNA vaccine is effective against breast cancer metastases. In the study presented here, we have further enhanced the efficacy of Mage-b vaccination through the improved delivery of the vaccine using recombinant Listeria monocytogenes (LM). Three overlapping fragments of Mage-b as well as the complete protein-encoding region of Mage-b have been expressed as a fusion protein with a truncated non-cytolytic form of listeriolysin O (LLO) in recombinant LM. These different Mage-b vaccine strains were preventively tested for their efficacy against breast cancer metastases in a syngeneic mouse tumour model 4T1. The LM-LLO-Mageb/2nd, expressing position 311 -660 of the cDNA of Mage-b, was the most effective vaccine strain against metastases in the 4T1 mouse breast tumour model. Vaccination with LM-LLO-Mage-b/2nd dramatically reduced the number of metastases by 96% compared with the saline group and by 88% compared with the vector control group (LM-LLO), and this correlated with strong Mage-b-specific CD8 T-cell responses in the spleen, after restimulation with Mage-b. However, no effect of LM-LLO-Mage-b/2nd was observed on 4T1 primary tumours, which may be the result of a complete absence of Mage-b-specific immune responses in the draining lymph nodes. Vaccination with LM-LLO-Mage-b/2nd could be an excellent follow-up after removal of the primary tumour, to eliminate metastases and residual tumour cells.

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“…Because of their restricted expression to germ cells and malignant tissues, there should be no deletion of a high-affinity T cell repertoire and theoretically a low risk of preexisting immune tolerance. Thus, the testis-restricted CT Ags are being used as targets in several vaccination trials (23). In particular, NY-ESO-1 and CT Ags belonging to the MAGE and GAGE families have been shown to elicit spontaneous cellular and/or humoral immune responses in cancer patients (24 -28).…”

Section: Ultiple Myeloma (Mm) 3 Is a B Cell Neoplasia Charac-mentioning

confidence: 99%

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

Condomines

Hose

Raynaud

et al. 2007

The Journal of Immunology

109

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Cancer-testis (CT) Ags are expressed in testis and malignant tumors but rarely in nongametogenic tissues. Due to this pattern, they represent attractive targets for cancer vaccination approaches. The aims of the present study are: 1) to assess the expression of CT genes on a pangenomic base in multiple myeloma (MM); 2) to assess the prognosis value of CT gene expression; and 3) to provide selection strategies for CT Ags in clinical vaccination trials. We report the expression pattern of CT genes in purified MM cells (MMC) of 64 patients with newly diagnosed MM and12 patients with monoclonal gammopathy of unknown significance, in normal plasma cell and B cell samples, and in 20 MMC lines. Of the 46 CT genes interrogated by the Affymetrix HG-U133 set arrays, 35 are expressed in the MMC of at least one patient. Of these, 25 are located on chromosome X. The expression of six CT genes is associated with a shorter event-free survival. The MMC of 98% of the patients express at least one CT gene, 86% at least two, and 70% at least three CT genes. By using a set of 10 CT genes including KM-HN-1, MAGE-C1, MAGE-A3/6/12, MAGE-A5, MORC, DDX43, SPACA3, SSX-4, GAGE-1–8, and MAGE-C2, a combination of at least three CT genes—desirable for circumventing tumor escape mechanisms—is obtained in the MMC of 67% of the patients. Provided that the immunogenicity of the products of these 10 CT genes is confirmed, gene expression profiling could be useful in identifying which CT Ags could be used to vaccinate a given patient.

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Tumoral and Immunologic Response After Vaccination of Melanoma Patients With an ALVAC Virus Encoding MAGE Antigens Recognized by T Cells

Cited by 163 publications

References 34 publications

Antigen-specificity and DTIC before peptide-vaccination differently shape immune-checkpoint expression pattern, anti-tumor functionality and TCR repertoire in melanoma patients

Antigen-specificity and DTIC before peptide-vaccination differently shape immune-checkpoint expression pattern, anti-tumor functionality and TCR repertoire in melanoma patients

Mage-b vaccine delivered by recombinant Listeria monocytogenes is highly effective against breast cancer metastases

Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis

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