Background: A new approach to prevent disease recurrence in high-risk melanoma patients involves immunization with gp100 and tyrosinase peptides. This is the first study to examine the effects of such treatments on ne...Background: A new approach to prevent disease recurrence in high-risk melanoma patients involves immunization with gp100 and tyrosinase peptides. This is the first study to examine the effects of such treatments on nevi. Design: We studied biopsies of ‘ clinically atypical’ nevi from 10 patients before and after peptide vaccination. All had a cutaneous melanoma measuring at least 1.5 mm in depth, satellite metastases, or at least one positive lymph node. We performed immunohistochemical stains for CD3, CD4, CD8, MHC-I, MHC-II, CD1a, HMB-45, MART-1, tyrosinase, bcl-2, p53, and Ki-67 (mib-1). Results: Immunohistochemistry showed no differences in staining due to vaccination in either the immunologic or melanocytic markers. However, there was a significant increase in both p53 and bcl-2 staining, and a trend toward decreased Ki-67 staining, in the nevi post-treatment. Discussion: The primary goal of peptide vaccinations with gp100 and tyrosinase is to activate melanoma-specific T cells in order to prevent melanoma recurrence. Nevi were studied in order to assess the effects on benign melanocytes. No significant changes in lymphocytes, langerhans cells, expression of MHC antigens, or melanocytic markers were found. The increase in p53 and bcl-2 raises the possibility that vaccination with melanocytic antigens stimulates a response in benign melanocytes.展开更多
研究酪氨酸激酶相关蛋白2(tyrosinase related protein 2,TRP-2)和gp100质粒DNA在B16黑色素瘤小鼠模型中的抗肿瘤作用。TRP-2及gp100在人类和鼠类黑色素瘤中均高度表达。鼠源gp100(mgp100)和鼠源TRP-2(mTRP-2)在小鼠中的免疫原性较差,...研究酪氨酸激酶相关蛋白2(tyrosinase related protein 2,TRP-2)和gp100质粒DNA在B16黑色素瘤小鼠模型中的抗肿瘤作用。TRP-2及gp100在人类和鼠类黑色素瘤中均高度表达。鼠源gp100(mgp100)和鼠源TRP-2(mTRP-2)在小鼠中的免疫原性较差,而异源黑色素瘤相关抗原可打破这些免疫耐受。使用电脉冲法免疫人源gp100(hgp100)和人源TRP-2(hTRP-2)质粒在B16F10肿瘤模型中表现出显著的保护作用。TRP-2和gp100质粒免疫结合Ii-PADRE(invariant Pan DR reactive epitope)和鼠源白介素-12(murine interleukin-12,mIL-12)质粒有效消退了建立的皮下B16F10肿瘤。上述结果表明,肌肉内注射异源DNA疫苗结合Ii-PADRE与IL-12质粒使用可能是一种有效治疗黑色素瘤的策略。展开更多
NY-ESO-1作为一种肿瘤抗原,具有较强的免疫抗原性,并且已成为肿瘤候选疫苗之一。但由于目前大多应用NY-ESO-1多肽以及蛋白质疫苗,其临床试验效果欠佳,亟需更为有效的NY-ESO-1抗原设计的肿瘤免疫治疗出现。该研究的目的是探索将NY-ESO-1...NY-ESO-1作为一种肿瘤抗原,具有较强的免疫抗原性,并且已成为肿瘤候选疫苗之一。但由于目前大多应用NY-ESO-1多肽以及蛋白质疫苗,其临床试验效果欠佳,亟需更为有效的NY-ESO-1抗原设计的肿瘤免疫治疗出现。该研究的目的是探索将NY-ESO-1与具有增强免疫效应的五种因子分别重组成嵌合蛋白抗原,使其更有效地被加工、转运和呈递,以期找到最佳的基因佐剂,增强NY-ESO-1作为肿瘤治疗性DNA疫苗的免疫效果。采用电脉冲体内细胞高效转入的方法对C57BL/6小鼠进行DNA免疫,发现用编码NY-ESO-1或连接有HSP70的嵌合体质粒免疫可诱导强烈的NY-ESO-1特异性Ig G1反应。NY-ESO-1连接泛素的质粒免疫小鼠主要诱导NY-ESO-1特异性Ig G2a反应,表明此基因佐剂诱导强的Th1免疫反应。与其他嵌合NY-ESO-1质粒免疫相比,NYESO-1连接泛素的质粒免疫小鼠,有效地保护小鼠对有NY-ESO-1表达的B16F10黑色素瘤细胞系的挑战作用,证明强的Th1免疫反应对预防和治疗肿瘤具有重要作用。去除调节性T细胞(regulatory T cells,Treg)可进一步增强泛素-NY-ESO-1嵌合DNA疫苗治疗黑色素瘤的作用。此外,Ub-NY-ESO-1质粒结合编码异源黑素瘤抗原GP100和TRP-2的质粒免疫可诱导对抗含有NY-ESO-1表达的B16F10黑色素瘤的协同抗肿瘤免疫疗效。该研究结果表明,编码泛素-NY-ESO-1嵌合抗原的质粒DNA疫苗或与编码其他相关黑色素瘤抗原的质粒的联合可能是有效的治疗黑色素瘤的疫苗。展开更多
文摘Background: A new approach to prevent disease recurrence in high-risk melanoma patients involves immunization with gp100 and tyrosinase peptides. This is the first study to examine the effects of such treatments on nevi. Design: We studied biopsies of ‘ clinically atypical’ nevi from 10 patients before and after peptide vaccination. All had a cutaneous melanoma measuring at least 1.5 mm in depth, satellite metastases, or at least one positive lymph node. We performed immunohistochemical stains for CD3, CD4, CD8, MHC-I, MHC-II, CD1a, HMB-45, MART-1, tyrosinase, bcl-2, p53, and Ki-67 (mib-1). Results: Immunohistochemistry showed no differences in staining due to vaccination in either the immunologic or melanocytic markers. However, there was a significant increase in both p53 and bcl-2 staining, and a trend toward decreased Ki-67 staining, in the nevi post-treatment. Discussion: The primary goal of peptide vaccinations with gp100 and tyrosinase is to activate melanoma-specific T cells in order to prevent melanoma recurrence. Nevi were studied in order to assess the effects on benign melanocytes. No significant changes in lymphocytes, langerhans cells, expression of MHC antigens, or melanocytic markers were found. The increase in p53 and bcl-2 raises the possibility that vaccination with melanocytic antigens stimulates a response in benign melanocytes.
文摘研究酪氨酸激酶相关蛋白2(tyrosinase related protein 2,TRP-2)和gp100质粒DNA在B16黑色素瘤小鼠模型中的抗肿瘤作用。TRP-2及gp100在人类和鼠类黑色素瘤中均高度表达。鼠源gp100(mgp100)和鼠源TRP-2(mTRP-2)在小鼠中的免疫原性较差,而异源黑色素瘤相关抗原可打破这些免疫耐受。使用电脉冲法免疫人源gp100(hgp100)和人源TRP-2(hTRP-2)质粒在B16F10肿瘤模型中表现出显著的保护作用。TRP-2和gp100质粒免疫结合Ii-PADRE(invariant Pan DR reactive epitope)和鼠源白介素-12(murine interleukin-12,mIL-12)质粒有效消退了建立的皮下B16F10肿瘤。上述结果表明,肌肉内注射异源DNA疫苗结合Ii-PADRE与IL-12质粒使用可能是一种有效治疗黑色素瘤的策略。
文摘NY-ESO-1作为一种肿瘤抗原,具有较强的免疫抗原性,并且已成为肿瘤候选疫苗之一。但由于目前大多应用NY-ESO-1多肽以及蛋白质疫苗,其临床试验效果欠佳,亟需更为有效的NY-ESO-1抗原设计的肿瘤免疫治疗出现。该研究的目的是探索将NY-ESO-1与具有增强免疫效应的五种因子分别重组成嵌合蛋白抗原,使其更有效地被加工、转运和呈递,以期找到最佳的基因佐剂,增强NY-ESO-1作为肿瘤治疗性DNA疫苗的免疫效果。采用电脉冲体内细胞高效转入的方法对C57BL/6小鼠进行DNA免疫,发现用编码NY-ESO-1或连接有HSP70的嵌合体质粒免疫可诱导强烈的NY-ESO-1特异性Ig G1反应。NY-ESO-1连接泛素的质粒免疫小鼠主要诱导NY-ESO-1特异性Ig G2a反应,表明此基因佐剂诱导强的Th1免疫反应。与其他嵌合NY-ESO-1质粒免疫相比,NYESO-1连接泛素的质粒免疫小鼠,有效地保护小鼠对有NY-ESO-1表达的B16F10黑色素瘤细胞系的挑战作用,证明强的Th1免疫反应对预防和治疗肿瘤具有重要作用。去除调节性T细胞(regulatory T cells,Treg)可进一步增强泛素-NY-ESO-1嵌合DNA疫苗治疗黑色素瘤的作用。此外,Ub-NY-ESO-1质粒结合编码异源黑素瘤抗原GP100和TRP-2的质粒免疫可诱导对抗含有NY-ESO-1表达的B16F10黑色素瘤的协同抗肿瘤免疫疗效。该研究结果表明,编码泛素-NY-ESO-1嵌合抗原的质粒DNA疫苗或与编码其他相关黑色素瘤抗原的质粒的联合可能是有效的治疗黑色素瘤的疫苗。
