更新于：2024-11-01

gp100 x MAGEA3

更新于：2024-11-01

基本信息

关联

项与 gp100 x MAGEA3 相关的药物

BVAC-M

靶点

MAGEA3 x gp100

作用机制

MAGEA3抑制剂 [+1]

在研机构-

原研机构

Cellid Co., Ltd.

在研适应症-

非在研适应症

黑色素瘤

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 gp100 x MAGEA3 相关的临床结果

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100 项与 gp100 x MAGEA3 相关的转化医学

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0 项与 gp100 x MAGEA3 相关的专利（医药）

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项与 gp100 x MAGEA3 相关的文献（医药）

2019-05-01·Cancer Immunology, Immunotherapy2区 · 医学

Natural T cell autoreactivity to melanoma antigens: clonally expanded melanoma-antigen specific CD8 + memory T cells can be detected in healthy humans

2区 · 医学

Article

作者: Li, Ruliang ; Roen, Diana R ; Zhang, Ting ; Mackiewicz, Andrzej ; Lehmann, Paul V ; Przybyla, Anna

We used four-color ImmunoSpot® assays, in conjunction with peptide pools that cover the sequence of tyrosinase (Tyr), melanoma-associated antigen A3 (MAGE-A3), melanocyte antigen/melanoma antigen recognized by T cells 1 (Melan-A/MART-1), glycoprotein 100 (gp100), and New York esophageal squamous cell carcinoma-1 (NY-ESO-1) to characterize the melanoma antigen (MA)-specific CD8 + cell repertoire in PBMC of 40 healthy human donors (HD). Tyr triggered interferon gamma (IFN-γ)-secreting CD8 + T cells in 25% of HD within 24 h of antigen stimulation ex vivo. MAGE-A3, Melan-A/MART-1, and gp100 also induced recall responses in 10%, 7.5%, and 2.5% of HD, respectively. At this time point, these CD8 + T cells did not yet produce GzB (granzyme B). However, they engaged in GzB production after 72 h of antigen stimulation. By this 72-h time point, 57.5% of the HD responded to at least one, and typically several, of the MA. A closer characterization of the Tyr-specific CD8 + T cell repertoire indicated that it was low-affinity, and to primarily entail a stem cell-like subpopulation. Collectively, our data reveal pre-existing endogenous T cell immunity against melanoma antigens in healthy donors, and analogous to natural autoantibodies, we have termed this "natural T cell autoreactivity".

2017-02-01·Journal of the European Academy of Dermatology and Venereology2区 · 医学

Melanoma antigens are biomarkers for ipilimumab response

2区 · 医学

Article

作者: Pavlikova, A. ; Fialova, A. ; Puzanov, I. ; Gkalpakiotis, S. ; Arenbergerova, M. ; Arenberger, P.

AbstractBackgroundNovel immunotherapy modalities significantly improve survival of patients with metastatic melanoma. However, CTLA‐4‐blocking monoclonal antibody ipilimumab is effective only in a small proportion of patients. Biomarkers for prediction of treatment response are indispensably needed.ObjectiveTo determine the utility of multimarker detection of circulating melanoma cells as prognostic and pharmacodynamic biomarker in patients with metastatic melanoma treated with ipilimumab.MethodsPatients (n = 62) with metastatic melanoma in unresectable stage III or metastatic stage IV treated with ipilimumab were recruited prospectively. The values of four melanoma markers on circulating cells Melan‐A, gp100, MAGE‐3 and melanoma inhibitory antigen prior to the treatment and within the therapy were compared to the data collected at baseline – after the melanoma surgery.ResultsThe immunotherapy pretreatment marker level was found to be prognostic of overall survival; lower levels were linked to longer survival time. Moreover, longitudinal follow‐up of melanoma markers in patients treated with ipilimumab correlates with therapy response. A decline of marker levels by >30% at week 6 (in 83% of the responding subjects) to week 9 (in all responders) of ipilimumab administration was associated with response to therapy. Elevation of the tumour markers during the treatment precedes clinical progression and gives an early warning of treatment failure.ConclusionMelanoma circulating cells hold potential as predictive and pharmacodynamic biomarker of immunotherapy.

2016-12-01·Journal for ImmunoTherapy of Cancer2区 · 医学

Single dose denileukin diftitox does not enhance vaccine-induced T cell responses or effectively deplete Tregs in advanced melanoma: immune monitoring and clinical results of a randomized phase II trial

2区 · 医学

ArticleOA

作者: Gajewski, Thomas F ; Zha, Yuanyuan ; Luke, Jason J ; Matijevich, Karen

BACKGROUNDDepletion of CD25(+) Tregs improves anti-tumor immunity in preclinical models. Denileukin diftitox is a recombinant fusion protein of human IL-2 and diptheria toxin fragment that also can kill CD25(+) T cells. Prior clinical trials of denileukin diftitox suggested reduction of FoxP3(+) Tregs and some clinical responses.METHODTo investigate the immunologic effects of denileukin difitox on vaccine-specific immune responses in melanoma, a randomized clinical trial of single dose denileukin diftitox prior to vaccination versus vaccination alone in subjects with HLA-A2(+) metastatic melanoma was performed. Treatment included randomization to a 4-peptide vaccine (Melan-A, gp100, MAGE3 and NA17 with GM-CSF emulsified in Montanide) alone or after single dose of denileukin diftitox (18 mcg/kg). Vaccine was given every 2 weeks for 3 doses and, absent clinical progression, continued every 2 weeks. Blood and tumor biopsies were obtained pretreatment and after 3 vaccinations for immunologic assessments.RESULTSIn 17 treated subjects there were no drug-related G3-4 adverse events. One partial response and 8 stable disease were observed in 9 subjects (4 DD: 5 vaccine only) with no impact of denileukin diftitox on time to progression. Total peripheral Tregs were not significantly altered, and in 1 patient biopsy intra-tumoral FoxP3 transcripts were not reduced following denileukin diftitox. ELISA for IL2R-α demonstrated no impact on outcomes by soluble CD25 level. Immune monitoring suggested the development of modest vaccine-specific CD8(+) T cell responses in the control group, however immunization efficacy was actually reduced in the denileukin diftitox group.CONCLUSIONOur results indicate that denileukin diftitox did not effectively deplete Tregs, augment T cell responses, or improve clinical activity in melanoma. Clinicaltrials.gov ID: NCT00515528; Registered August 9, 2007.