Palucka A Karolina, Dhodapkar Madhav V, Paczesny Sophie, Burkeholder Susan, Wittkowski Knut M, Steinman Ralph M, Fay Joseph, Banchereau Jacques
Baylor Institute for Immunology Research, 3434 Live Oak, Dallas, Texas 75204, USA.
J Immunother. 2003 Sep-Oct;26(5):432-9. doi: 10.1097/00002371-200309000-00006.
There is evidence that dendritic cell (DC) vaccines induce tumor-specific immune responses that correlate with clinical responses. Little is known, however, about the kinetics of T-cell responses to antigens presented on DC vaccines. The authors vaccinated 18 HLA A*0201+ patients with stage IV melanoma with CD34 HPC-derived DCs pulsed with six antigens: influenza matrix peptide (Flu-MP), KLH, and peptides derived from the four melanoma antigens: MART-1/Melan A, gp100, tyrosinase, and MAGE-3. A single DC vaccination was sufficient for induction of KLH-specific CD4 T-cell responses in five patients and Flu-MP-specific CD8 T-cell responses in eight patients. A single DC vaccine was sufficient for induction of tumor-specific effectors to at least one melanoma antigen in five patients. Thus, a single injection of CD34 HPC-derived DCs can lead to rapid immune response to CD4 epitopes or to melanoma antigens.
有证据表明,树突状细胞(DC)疫苗可诱导与临床反应相关的肿瘤特异性免疫反应。然而,对于T细胞对DC疫苗所呈递抗原的反应动力学知之甚少。作者用六种抗原脉冲处理的CD34造血祖细胞来源的DC,对18例IV期黑色素瘤的HLA A*0201+患者进行疫苗接种,这六种抗原分别为:流感基质肽(Flu-MP)、钥孔血蓝蛋白(KLH)以及四种黑色素瘤抗原衍生的肽:黑色素瘤抗原识别分子-1/黑色素A(MART-1/Melan A)、糖蛋白100(gp100)、酪氨酸酶和黑色素瘤相关抗原-3(MAGE-3)。单次DC疫苗接种足以在5例患者中诱导出针对KLH的特异性CD4 T细胞反应,并在8例患者中诱导出针对Flu-MP的特异性CD8 T细胞反应。单次DC疫苗接种足以在5例患者中诱导出针对至少一种黑色素瘤抗原的肿瘤特异性效应细胞。因此,单次注射CD34造血祖细胞来源的DC可导致对CD4表位或黑色素瘤抗原的快速免疫反应。