This study is being done to evaluate the safety and the clinical activity of MAGE-A3 Antigen-Specific Cancer Immunotherapeutic in patients with unresectable and progressive metastatic cutaneous melanoma.

开始日期2008-09-29

申办/合作机构

GSK Plc

100 项与 Recombinant MAGE-A3 protein immunotherapy(GlaxoSmithKline Plc) 相关的临床结果

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100 项与 Recombinant MAGE-A3 protein immunotherapy(GlaxoSmithKline Plc) 相关的转化医学

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100 项与 Recombinant MAGE-A3 protein immunotherapy(GlaxoSmithKline Plc) 相关的专利（医药）

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项与 Recombinant MAGE-A3 protein immunotherapy(GlaxoSmithKline Plc) 相关的文献（医药）

2021-08-01·Cancer Immunology, Immunotherapy2区 · 医学

Characterization and comparison of innate and adaptive immune responses at vaccine sites in melanoma vaccine clinical trials

2区 · 医学

Article

作者: Deacon, Donna H ; Slingluff, Craig L ; Koeppel, Alexander F ; Meneveau, Max O ; Pollack, Karlyn E ; Turner, Stephen D ; Petroni, Gina R ; Melssen, Marit M ; Hickman, Alexandra ; Sol-Church, Katia ; Smolkin, Mark E ; Pinczewski, Joel

The strength and durability of systemic anti-tumor immune responses induced by cancer vaccines depends on adjuvants to support an immunogenic vaccine site microenvironment (VSME). Adjuvants include water-in-oil emulsions with incomplete Freund's adjuvant (IFA) and combinations of toll-like receptor (TLR) agonists, including a preparation containing TLR4 and TLR9 agonists with QS-21 (AS15). IFA-containing vaccines can promote immune cell accumulation at the VSME, whereas effects of AS15 are largely unexplored. Therefore, we assessed innate and adaptive immune cell accumulation and gene expression at the VSME after vaccination with AS15 and compared to effects with IFA. We hypothesized that AS15 would promote less accumulation of innate and adaptive immune cells at the VSME than IFA vaccines. In two clinical trials, patients with resected high-risk melanoma received either a multipeptide vaccine with IFA or a recombinant MAGE-A3 protein vaccine with AS15. Vaccine site biopsies were obtained after one or multiple vaccines. T cells accumulated early after vaccines with AS15, but this was not durable or of the same magnitude as vaccination in IFA. Vaccines with AS15 increased durable expression of DC- and T cell-related genes, as well as PD-L1 and IDO1, suggesting complex activation and regulation of innate and adaptive immune function with AS15. These changes were generally greater with vaccines containing IFA, but IFA induced reduction in myeloid suppressor cells markers. Evidence of tertiary lymphoid structure (TLS) formation was observed with both adjuvants. Our findings highlight adjuvant-dependent changes in immune features at the VSME that may impact systemic immune responses.

2018-12-01·BMC Cancer2区 · 医学

A phase II trial of recombinant MAGE-A3 protein with immunostimulant AS15 in combination with high-dose Interleukin-2 (HDIL2) induction therapy in metastatic melanoma

2区 · 医学

ArticleOA

作者: Vence, Luis M ; McQuade, Jennifer L ; Torres-Cabala, Carlos A ; James, Marihella L ; Hwu, Wen-Jen ; Bassett, Roland ; Homsi, Jade ; Popuri, Rashmi Murthy

BACKGROUNDHDIL-2 is approved for advanced melanoma based on its durable antitumor activity. MAGE-A3 cancer immunotherapeutic (MAGE-A3 CI) is a recombinant MAGE-A3 protein combined with an immunostimulant adjuvant system and has shown antitumor activity in melanoma. We assessed the safety and anti-tumor activity of HDIL-2 combined with MAGE-A3 CI in advanced melanoma.METHODSPatients with unresectable Stage III or Stage IV MAGE-A3-positive melanoma were enrolled in this phase II study. Treatment included an induction phase of MAGE-A3 CI plus HDIL-2 for 8 cycles followed by a maintenance phase of MAGE-A3 CI monotherapy. The primary endpoints were safety and objective response assessed per RECIST v1.1. Immune biomarker and correlative studies on tumor and peripheral blood were performed.RESULTSEighteen patients were enrolled. Seventeen patients were evaluable for safety and sixteen for response. Responses occurred in 4/16 (25%) patients with 3 complete responses, and stable disease in 6/16 (38%) patients with a disease control rate of 63%. The median duration of response was not reached at median follow-up of 36.8 months. Induction therapy of HDIL-2 + MAGE-A3 CI had similar toxicities to those reported with HDIL-2 alone. Maintenance MAGE-A3 monotherapy was well-tolerated. Increased immune checkpoint receptor expression by circulating T regulatory cells was associated with poor clinical outcomes; and responders tended to have increased tumor infiltrating T cells in the baseline tumor samples.CONCLUSIONSThe safety profile of HDIL-2 + MAGE-A3 CI was similar to HDIL-2 monotherapy. Maintenance MAGE-A3 CI provides robust anti-tumor activity in patients who achieved disease control with induction therapy. Immune monitoring data suggest that MAGE-A3 CI plus checkpoint inhibitors could be a promising treatment for MAGE-A3-positive melanoma.TRIAL REGISTRATIONClinicalTrials.gov, NCT01266603 . Registered 12/24/2010, https://clinicaltrials.gov/ct2/show/NCT01266603.

2016-01-01·Cancer Immunology, Immunotherapy2区 · 医学

A randomized pilot trial testing the safety and immunologic effects of a MAGE-A3 protein plus AS15 immunostimulant administered into muscle or into dermal/subcutaneous sites

2区 · 医学

Article

作者: Smolkin, Mark E ; Varhegyi, Nikole E ; Petroni, Gina R ; Galeassi, Nadejda V ; Scott, Kristy ; Reed, Caroline M ; Slingluff, Craig L ; Deacon, Donna H ; Olson, Walter C ; Grosh, William W ; Chianese-Bullock, Kimberly A ; Donnelly, Sean B ; Smith, Kelly T ; Mauldin, Ileana S

INTRODUCTIONMethods to induce T cell responses to protein vaccines have not been optimized. The immunostimulant AS15 has been administered with the recombinant MAGE-A3 protein (recMAGE-A3) i.m. but not i.d. or s.c. This study tests hypotheses that the i.d./s.c. route is safe and will increase CD4(+) and CD8(+) T cell responses to MAGE-A3.PATIENTS AND METHODSTwenty-five patients with resected stage IIB-IV MAGE-A3(+) melanoma were randomized to immunization with recMAGE-A3 combined with AS15 immunostimulant (MAGE-A3 immunotherapeutic) either i.m. (group A, n = 13) or i.d./s.c. (group B, n = 12). Adverse events were recorded. Ab responses to MAGE-A3 were measured by ELISA. T cell responses to overlapping MAGE-A3 peptides were assessed in PBMC and a sentinel immunized node (SIN) after 1 in vitro stimulation with recMAGE-A3, by IFN-γ ELISPOT assay and by flow cytometry for multifunctional (TNF-α/IFN-γ) responses.RESULTSBoth routes of immunization were well tolerated without treatment-related grade 3 adverse events. All patients had durable Ab responses. For all 25 patients, the T cell response rate by ELISPOT assay was 30 % in SIN (7/23) but only 4 % (1/25) in PBMC. By flow cytometry, multifunctional CD8(+) T cell responses were identified in one patient in each group; multifunctional CD4(+) T cell response rates for groups A and B, respectively, were 31 and 64 % in SIN and 31 and 50 % in PBMC.CONCLUSIONThe MAGE-A3 immunotherapeutic was well tolerated after i.d./s.c. administration, with trends to higher CD4(+) T cell response rates than with i.m. administration. This study supports further study of AS15 by i.d./s.c. administration.

100 项与 Recombinant MAGE-A3 protein immunotherapy(GlaxoSmithKline Plc) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
膀胱癌	临床2期	-	GSK Plc	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00706238 (CTgov)	临床2期	转移性黑色素瘤 \| MAGE-A3阳性肌层浸润性膀胱癌	5	GSK Biologicals' Recombinant MAGE-A3 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK1203486A	窪艱網廠淵蓋膚鹽選網(淵鏇齋鹹襯壓築齋鹽蓋) = 簾醖餘積構鬱簾積獵鑰願遞構製顧鹹齋鹹廠窪 (鹽襯廠蓋願艱衊餘遞襯, 製網鹽範積築壓構製衊 ~ 鹽齋積壓鑰艱鬱廠範憲) 更多	-	2019-06-03
ASCO2008 人工标引	临床2期	转移性黑色素瘤	75	MAGE-A3 protein + AS15	(製醖襯鑰鹹鹹鏇構鏇壓) = 憲鬱淵醖艱膚顧糧範願鹽窪艱衊齋範構壓鑰鏇 (夢齋淵範製構醖憲鹹衊 ) 更多	积极	2008-05-20
ASCO2008 人工标引	临床2期	转移性黑色素瘤	75	MAGE-A3 protein + AS02B	(製醖襯鑰鹹鹹鏇構鏇壓) = 壓膚築鑰齋繭襯廠鹹構鹽窪艱衊齋範構壓鑰鏇 (夢齋淵範製構醖憲鹹衊 ) 更多	积极	2008-05-20
ASCO2008	临床2期	非小细胞肺癌辅助	182	MAGE-A3 recombinant protein + Adjuvant System	(顧鹹製壓觸鹽遞廠艱鬱) = 構蓋艱鹹廠構醖衊構遞鹹選網廠壓衊簾糧襯獵 (窪襯範壓製觸襯夢壓齋 )	-	2008-05-20