A Study in Metastatic Melanoma Using a Lymphodepleting Conditioning Followed by Infusion of Anti-MART-1 TCR-Gene Engineered Lymphocytes and Subsequent Peptide Immunization

RATIONALE: Inserting a laboratory-treated gene into a person's white blood cells may make the body build an immune response to kill tumor cells. Giving cyclophosphamide and fludarabine before a white blood cell infusion may suppress the immune system and allow tumor cells to be killed. Vaccines may make the body build an immune response to kill tumor cells. Aldesleukin may stimulate a person's white blood cells to kill tumor cells. Combining white blood cell infusion with vaccine therapy and aldesleukin may cause a stronger immune response and kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of gene-modified white blood cells when given together with cyclophosphamide, fludarabine, vaccine therapy, and aldesleukin and to see how well it works in treating patients with metastatic melanoma.

开始日期2004-07-01

申办/合作机构

National Institutes of Health Clinical Center

[+1]

NCT00006243 / CompletedN/AIIT

Melanoma Vaccines: Differentiation Antigen Peptides (MART-1:27-35, Tyrosinase and Gp-100) as Immune Targets

This randomized pilot clinical trial studies vaccine therapy and sargramostim in treating patients with stage IV malignant melanoma. Vaccines made from melanoma peptides or antigens may help the body build an effective immune response to kill tumor cells. Colony-stimulating factors, such as sargramostim, increase the number of white blood cells and platelets found in bone marrow or peripheral blood. Giving vaccine therapy together with sargramostim may be an effective treatment for malignant melanoma

开始日期2000-10-01

申办/合作机构

National Cancer Institute

100 项与 MART-1:27-35 peptide vaccine(NCI) 相关的临床结果

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100 项与 MART-1:27-35 peptide vaccine(NCI) 相关的转化医学

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项与 MART-1:27-35 peptide vaccine(NCI) 相关的文献（医药）

2017-09-01·Clinical Cancer Research1区 · 医学

Immune Correlates of GM-CSF and Melanoma Peptide Vaccination in a Randomized Trial for the Adjuvant Therapy of Resected High-Risk Melanoma (E4697)

1区 · 医学

Article

作者: Cohen, Gary I. ; Zhao, Fengmin ; Lee, Sandra ; Atkins, Michael B. ; Tarhini, Ahmad A. ; Butterfield, Lisa H. ; Whiteside, Theresa L. ; Lawson, David H. ; Kirkwood, John M. ; White, Richard L. ; Margolin, Kim A.

AbstractPurpose: E4697 was a multicenter intergroup randomized placebo-controlled phase III trial of adjuvant GM-CSF and/or a multiepitope melanoma peptide vaccine for patients with completely resected, high-risk stage III/IV melanoma.Experimental Design: A total of 815 patients were enrolled from December 1999 to October 2006 into this six-arm study. GM-CSF was chosen to promote the numbers and functions of dendritic cells (DC). The melanoma antigen peptide vaccine (Tyrosinase368-376 (370D), gp100209-217 (210M), MART-127-35) in montanide was designed to promote melanoma-specific CD8+ T-cell responses.Results: Although the overall RFS and OS were not significantly improved with the vaccine or GM-CSF when compared with placebo, immunomodulatory effects were observed in peripheral blood and served as important correlates to this therapeutic study. Peripheral blood was examined to evaluate the impact of GM-CSF and/or the peptide vaccine on peripheral blood immunity and to investigate potential predictive or prognostic biomarkers. A total of 11.3% of unvaccinated patients and 27.1% of vaccinated patients developed peptide-specific CD8+ T-cell responses. HLA-A2+ patients who had any peptide-specific CD8+ T-cell response at day +43 tended to have poorer OS in univariate analysis. Patients receiving GM-CSF had significant reduction in percentages of circulating myeloid dendritic cells (mDC) and plasmacytoid DC (pDC) at day +43. In a subset of patients who received GM-CSF, circulating myeloid-derived suppressor cells (MDSC), and anti-GM-CSF–neutralizing antibodies (Nabs) were also modulated. The majority of patients developed anti-GM-CSF Nabs, which correlated with improved RFS and OS.Conclusions: The assessment of cellular and humoral responses identified counterintuitive immune system changes correlating with clinical outcome. Clin Cancer Res; 23(17); 5034–43. ©2017 AACR.

2009-10-01·Clinical Cancer Research1区 · 医学

Dendritic Cell Vaccination Combined with CTLA4 Blockade in Patients with Metastatic Melanoma

1区 · 医学

Article

作者: Straatsma, Bradley R. ; Ochoa, Maria Teresa ; Hui, Liu ; de la Rocha, Pilar ; Ribas, Antoni ; Chmielowski, Bartosz ; Jalil, Jason ; Marincola, Francesco M. ; Oseguera, Denise K. ; Comin-Anduix, Begoña ; Cochran, Alistair J. ; Villanueva, Arturo ; Economou, James S. ; Glaspy, John A. ; Wang, Ena ; Gomez-Navarro, Jesus ; Seja, Elizabeth ; McCannel, Tara A.

AbstractPurpose: Tumor antigen–loaded dendritic cells (DC) are believed to activate antitumor immunity by stimulating T cells, and CTL-associated antigen 4 (CTLA4)–blocking antibodies should release a key negative regulatory pathway on T cells. The combination was tested in a phase I clinical trial in patients with advanced melanoma.Experimental Design: Autologous DC were pulsed with MART-126-35 peptide and administered with a dose escalation of the CTLA4-blocking antibody tremelimumab. Sixteen patients were accrued to five dose levels. Primary end points were safety and immune effects; clinical efficacy was a secondary end point.Results: Dose-limiting toxicities of grade 3 diarrhea and grade 2 hypophysitis developed in two of three patients receiving tremelimumab at 10 mg/kg monthly. Four patients had an objective tumor response, two partial responses and two complete responses, all melanoma free between 2 and 4 years after study initiation. There was no difference in immune monitoring results between patients with an objective tumor response and those without a response. Exploratory gene expression analysis suggested that immune-related gene signatures, in particular for B-cell function, may be important in predicting response.Conclusion: The combination of MART-1 peptide–pulsed DC and tremelimumab results in objective and durable tumor responses at the higher range of the expected response rate with either agent alone. (Clin Cancer Res 2009;15(19):6267–76)

2008-12-01·Journal of Translational Medicine2区 · 医学

Validation of a HLA-A2 tetramer flow cytometric method, IFNgamma real time RT-PCR, and IFNgamma ELISPOT for detection of immunologic response to gp100 and MelanA/MART-1 in melanoma patients

2区 · 医学

ArticleOA

作者: Yuanxin Xu ; Susan M Richards ; Kathleen DePalma ; Valerie Theobald ; Keirsten Seiger ; Michael A Perricone ; Laura Atwater ; Crystal Sung

BACKGROUNDHLA-A2 tetramer flow cytometry, IFNgamma real time RT-PCR and IFNgamma ELISPOT assays are commonly used as surrogate immunological endpoints for cancer immunotherapy. While these are often used as research assays to assess patient's immunologic response, assay validation is necessary to ensure reliable and reproducible results and enable more accurate data interpretation. Here we describe a rigorous validation approach for each of these assays prior to their use for clinical sample analysis.METHODSStandard operating procedures for each assay were established. HLA-A2 (A*0201) tetramer assay specific for gp100209(210M) and MART-126-35(27L), IFNgamma real time RT-PCR and ELISPOT methods were validated using tumor infiltrating lymphocyte cell lines (TIL) isolated from HLA-A2 melanoma patients. TIL cells, specific for gp100 (TIL 1520) or MART-1 (TIL 1143 and TIL1235), were used alone or spiked into cryopreserved HLA-A2 PBMC from healthy subjects. TIL/PBMC were stimulated with peptides (gp100209, gp100pool, MART-127-35, or influenza-M1 and negative control peptide HIV) to further assess assay performance characteristics for real time RT-PCR and ELISPOT methods. Validation parameters included specificity, accuracy, precision, linearity of dilution, limit of detection (LOD) and limit of quantification (LOQ). In addition, distribution was established in normal HLA-A2 PBMC samples. Reference ranges for assay controls were established.RESULTSThe validation process demonstrated that the HLA-A2 tetramer, IFNgamma real time RT-PCR, and IFNgamma ELISPOT were highly specific for each antigen, with minimal cross-reactivity between gp100 and MelanA/MART-1. The assays were sensitive; detection could be achieved at as few as 1/4545-1/6667 cells by tetramer analysis, 1/50,000 cells by real time RT-PCR, and 1/10,000-1/20,000 by ELISPOT. The assays met criteria for precision with %CV < 20% (except ELISPOT using high PBMC numbers with %CV < 25%) although flow cytometric assays and cell based functional assays are known to have high assay variability. Most importantly, assays were demonstrated to be effective for their intended use. A positive IFNgamma response (by RT-PCR and ELISPOT) to gp100 was demonstrated in PBMC from 3 melanoma patients. Another patient showed a positive MART-1 response measured by all 3 validated methods.CONCLUSIONOur results demonstrated the tetramer flow cytometry assay, IFNgamma real-time RT-PCR, and INFgamma ELISPOT met validation criteria. Validation approaches provide a guide for others in the field to validate these and other similar assays for assessment of patient T cell response. These methods can be applied not only to cancer vaccines but to other therapeutic proteins as part of immunogenicity and safety analyses.

100 项与 MART-1:27-35 peptide vaccine(NCI) 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
皮肤黑色素瘤	临床1期	美国	National Institutes of Health Clinical Center	2004-07-01
转移性黑色素瘤	临床1期	美国	National Institutes of Health Clinical Center	2004-07-01

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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


AACR2011	N/A	黑色素瘤	12	Vaccination with MART-1 (27-35), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) peptides given in-oil-adjuvant with TLR-9 agonist PF-3512676 and GMCSF	(構選餘繭鏇簾齋廠鹽築) = 鹽顧齋蓋蓋繭鑰願餘鏇願餘鹹鏇憲鑰鬱鹽獵製 (網觸壓襯選獵憲醖遞範 ) 更多	-	2011-04-15