Recombinant NY‐ESO‐1 Cancer Antigen: Production and Purification under cGMP Conditions

Murphy, Roger; Green, S.; Ritter, Gerd; Cohen, Lawrence E.; Ryan, David; Woods, Wayne G.; Rubira, Michael R.; Cebon, Jonathan; Davis, Ian D.; Sjölander, Anders; Kypridis, A.; Kalnins, H.; McNamara, Michael; Moloney, M B; Ackland, James; Cartwright, Glenn A.; Rood, Julian I.; Dumsday, Geoff; Healey, K; Maher, Darryl; Maraskovsky, Eugene; Chen, Y.‐T.; Hoffman, Eric W.; Old, Lloyd J.; Scott, Andrew M.

doi:10.1081/pb-200054732

Cited by 39 publications

(28 citation statements)

References 19 publications

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“…34 Endotoxin levels ranged between 3 and 31 EU/0.1 mg of protein (limit Ͻ 175 EU/0.1 mg protein). Formulated NY-ESO-1/ ISCOMATRIX vaccine was generated whereby NY-ESO-1 antigen was physically incorporated into ISCOMATRIX particles as described, 33 and the protein concentration was determined by amino acid analysis.…”

Section: Generation Of Recombinant Ny-eso-1 and Melan-a Formulationsmentioning

confidence: 99%

“…28 Third, the Melan-A [26][27][28][29][30][31][32][33][34][35] /HLA-A2 epitope is generated and presented by HLA-A2 ϩ melanoma cells, and these are efficiently lysed by Melan-A [26][27][28][29][30][31][32][33][34][35] /HLA-A2-specific CTLs. 29 Finally, the Melan-A [26][27][28][29][30][31][32][33][34][35] /HLA-A2 epitope is generated by conventional proteasomes but may be destroyed by immunoproteasomes expressed by DCs or by interferon-␥ (IFN-␥)-treated tumor cells. 30 This final point makes the development of a Melan-A protein vaccine problematic as immunoproteasome-expressing DCs will fail to generate tumor-relevant CTLs in vivo, thus restricting the development of a Melan-A vaccine to peptide-based strategies, which have shown limited clinical efficacy because of multiple tumor escape mechanisms.…”

Section: Introductionmentioning

confidence: 99%

“…26 In contrast, Melan-A is unusual. First, a large proportion of healthy human leukocyte associated-A2 (HLA-A2)-restricted individuals possess naive CD8 ϩ T cells specific for the naturally presented Melan-A [26][27][28][29][30][31][32][33][34][35] /HLA-A2 epitope. 27 Second, the Melan-A [26][27][28][29][30][31][32][33][34][35] /HLA-A2 epitope is strikingly immunodominant with few other CD8 ϩ T-cell epitopes described.…”

Section: Introductionmentioning

confidence: 99%

“…First, a large proportion of healthy human leukocyte associated-A2 (HLA-A2)-restricted individuals possess naive CD8 ϩ T cells specific for the naturally presented Melan-A [26][27][28][29][30][31][32][33][34][35] /HLA-A2 epitope. 27 Second, the Melan-A [26][27][28][29][30][31][32][33][34][35] /HLA-A2 epitope is strikingly immunodominant with few other CD8 ϩ T-cell epitopes described. 28 Third, the Melan-A [26][27][28][29][30][31][32][33][34][35] /HLA-A2 epitope is generated and presented by HLA-A2 ϩ melanoma cells, and these are efficiently lysed by Melan-A [26][27][28][29][30][31][32][33][34][35] /HLA-A2-specific CTLs.…”

Section: Introductionmentioning

confidence: 99%

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Processing and cross-presentation of individual HLA-A, -B, or -C epitopes from NY-ESO-1 or an HLA-A epitope for Melan-A differ according to the mode of antigen delivery

Robson

McAlpine

Knights

et al. 2010

Blood

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The ability of dendritic cells (DCs) to cross-present protein tumor antigens to cytotoxic T lymphocytes (CTLs) underpins the success of therapeutic cancer vaccines. We studied cross-presentation of the cancer/testis antigen, NY-ESO-1, and the melanoma differentiation antigen, Melan-A by human DC subsets. Monocyte-derived DCs (MoDCs) efficiently cross-presented human leukocyte associated (HLA)–A2-restricted epitopes from either a formulated NY-ESO-1/ISCOMATRIX vaccine or when either antigen was mixed with ISCOMATRIX adjuvant. HLA-A2 epitope generation required endosomal acidification and was proteasome-independent for NY-ESO-1 and proteasome-dependent for Melan-A. Both MoDCs and CD1c+ blood DCs cross-presented NY-ESO-1–specific HLA-A2157-165–, HLA-B760-72–, and HLA-Cw392-100–restricted epitopes when formulated as an NY-ESO-1/ISCOMATRIX vaccine, but this was limited when NY-ESO-1 and ISCOMATRIX adjuvant were added separately to the DC cultures. Finally, cross-presentation of NY-ESO-1157-165/HLA-A2, NY-ESO-160-72/HLA-B7, and NY-ESO-192-100/HLA-Cw3 epitopes was proteasome-dependent when formulated as immune complexes (ICs) but only proteasome-dependent for NY-ESO-160-72/HLA-B7–restricted cross-presentation facilitated by ISCOMATRIX adjuvant. We demonstrate, for the first time, proteasome-dependent and independent cross-presentation of HLA-A–, B–, and C–restricted epitopes within the same full-length tumor antigen by human DCs. Our findings identify important differences in the capacities of human DC subsets to cross-present clinically relevant, full-length tumor antigens and how vaccine formulation impacts CTL responses in vivo.

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Section: Generation Of Recombinant Ny-eso-1 and Melan-a Formulationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Processing and cross-presentation of individual HLA-A, -B, or -C epitopes from NY-ESO-1 or an HLA-A epitope for Melan-A differ according to the mode of antigen delivery

Robson

McAlpine

Knights

et al. 2010

Blood

View full text Add to dashboard Cite

show abstract

“…9 The NY-ESO-1 ISCOMATRIXV R Vaccine consists of 200 lg/mL of recombinant NY-ESO-1 protein and 240 lg/mL ISCOMATRIXV R adjuvant in 0.65 mL. The administered dose was 100 lg NY-ESO-1 protein formulated with 120 lg ISCOMATRIXV R adjuvant (0.5 mL administered intramuscularly).…”

Section: Vaccine Productionmentioning

confidence: 99%

NY‐ESO‐1 specific antibody and cellular responses in melanoma patients primed with NY‐ESO‐1 protein in ISCOMATRIX and boosted with recombinant NY‐ESO‐1 fowlpox virus

Chen

Dawoodji

Tarlton

et al. 2014

Intl Journal of Cancer

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Vaccination strategies based on repeated injections of NY-ESO-1 protein formulated in ISCOMATRIX particles (NY-ESO-1 ISCOMATRIX) have shown to elicit combined NY-ESO-1 specific antibody and T cell responses. However, it remains unclear whether heterologous prime-boost strategies based on the combination with NY-ESO-1 ISCOMATRIX with different NY-ESO-1 boosting reagents could be used to increase NY-ESO-1 CD8 1 or CD4 1 T cell responses. To address this question, we carried out a randomized clinical trial in 39 high-risk, resected melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX, and then boosted with repeated injections of either recombinant fowlpox virus encoding full length NY-ESO-1 (rF-NY-ESO-1) (Arm A) or NY-ESO-1 ISCOMATRIX alone (Arm B). We have comprehensively analyzed NY-ESO-1 specific T cells and B cells response in all patients before and after vaccination for a total of seven time points per patient. NY-ESO-1 ISCOMATRIX alone elicited a strong NY-ESO-1 specific CD4 1 T cell and antibody response, which was maintained by both regiments at similar levels. Current vaccination strategies based on the use of recombinant viruses are failing to elicit specific T-cell responses similar to those generated by natural infections. The limited success of recombinant viruses as delivery vectors for T cell vaccines is mainly due to their high immunogenicity, resulting in an overwhelming immune response focused on the viral-vector proteins rather than on the desired recombinant protein antigens. 1 However, it remains unclear whether recombinant viruses can be used to boost the magnitude of immune responses elicited by the prior injection of recombinant immunogenic proteins.The cancer-testis antigen NY-ESO-1 is an attractive target antigen for cancer therapy, as it is expressed in many cancer types, but not normal tissues, except testis.2 Although promising results in various NY-ESO-1 formulations have been reported in recent cancer vaccine studies, 3-6 the optimal strategy for generating integrated antibody and T cell responses to control tumor growth has yet to be determined.ISCOMATRIX adjuvant is comprised of saponin, cholesterol and phospholipid and is capable of associating with proteins to form ISCOMATRIX vaccines.7 Recombinant

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Reduction of plasma urate levels following treatment with multiple doses of pegloticase (polyethylene glycol–conjugated uricase) in patients with treatment‐failure gout: Results of a phase II randomized study

Sundy

Becker

Baraf

et al. 2008

Arthritis & Rheumatism

161

127

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Objective. To assess the efficacy of pegloticase in achieving and maintaining plasma urate levels of <6 mg/dl in gout patients in whom other treatments have failed, and to assess the pharmacokinetics and safety of pegloticase.Methods. Forty-one patients were randomized to undergo 12-14 weeks of treatment with pegloticase at 1 of 4 dosage levels: 4 mg every 2 weeks, 8 mg every 2 weeks, 8 mg every 4 weeks, or 12 mg every 4 weeks. Plasma uricase activity, plasma urate, and antipegloticase antibodies were measured, pharmacokinetic parameters were assessed, and adverse events were recorded.Results. The mean plasma urate level was reduced to <6 mg/dl within 6 hours in all dosage groups, and this was sustained throughout the treatment period in the 8 mg and 12 mg dosage groups. The most effective dosage was 8 mg every 2 weeks. Twenty-six patients received all protocol doses. The percentage of the patients in whom the primary efficacy end point (plasma urate <6 mg/dl for 80% of the study period) was achieved ranged from 50% to 88%. Gout flares occurred in 88% of the patients. The majority of adverse events (excluding gout flare) were unrelated to treatment and were mild or moderate in severity. Infusion-day adverse events were the most common reason for study withdrawal (12 of 15 withdrawals). There were no anaphylactic reactions. Antipegloticase antibody, present in 31 of 41 patients, was associated with reduced circulating half-life of pegloticase in some patients.Conclusion. Pegloticase, administered in multiple doses, was effective in rapidly reducing and maintaining plasma urate levels at <6 mg/dl in most patients in whom conventional therapy had been unsuccessful due to lack of response, intolerability, or contraindication.ClinicalTrials.gov identifier: NCT00080210.

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Recombinant NY‐ESO‐1 Cancer Antigen: Production and Purification under cGMP Conditions

Cited by 39 publications

References 19 publications

Processing and cross-presentation of individual HLA-A, -B, or -C epitopes from NY-ESO-1 or an HLA-A epitope for Melan-A differ according to the mode of antigen delivery

Processing and cross-presentation of individual HLA-A, -B, or -C epitopes from NY-ESO-1 or an HLA-A epitope for Melan-A differ according to the mode of antigen delivery

NY‐ESO‐1 specific antibody and cellular responses in melanoma patients primed with NY‐ESO‐1 protein in ISCOMATRIX and boosted with recombinant NY‐ESO‐1 fowlpox virus

Reduction of plasma urate levels following treatment with multiple doses of pegloticase (polyethylene glycol–conjugated uricase) in patients with treatment‐failure gout: Results of a phase II randomized study

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