Tagawa Scott T, Lee Peter, Snively Jolie, Boswell William, Ounpraseuth Song, Lee Sandra, Hickingbottom Barbara, Smith John, Johnson Denise, Weber Jeffrey S
Department of Medicine, Keck-University of Southern California School of Medicine, Los Angeles, California, USA.
Cancer. 2003 Jul 1;98(1):144-54. doi: 10.1002/cncr.11462.
Based on the likelihood of transfecting large numbers of local antigen-presenting cells, a Phase I study in patients with Stage IV melanoma was conducted to determine the practicality, toxicity of, and immune responses to repeated infusions into a groin lymph node of escalating doses of a DNA plasmid encoding tyrosinase epitopes.
Cohorts of 8 patients each received 200 microg, 400 microg, or 800 microg of DNA intranodally by pump over 96 hours every 14 days for 4 cycles. Blood was collected for immunologic assays and to measure plasmid in serum prior to treatment, 4 weeks later, and 8 weeks later. Scans and X-rays were performed at baseline and after 8 weeks.
Treatment was tolerated well, with only five patients demonstrating Grade 1-2 toxicity. Vaccine delivery by 96-hour infusions of plasmid into a groin lymph node resulted in only 1 episode of catheter leakage in 107 cannulations. Detection of plasmid in serum was rare and transient in two patients. Immune responses by peptide-tetramer assay to tyrosinase 207-216 were detected in 11 of 26 patients. No clinical responses were seen. Survival of the heavily pretreated patients on this trial was unexpectedly long, with 16 of 26 patients alive at a median follow-up of 12 months.
Infusion of a DNA plasmid vaccine into a groin lymph node was practical and well tolerated. Immune responses to a novel tyrosinase epitope were noted. Overall survival in this trial of heavily pretreated patients was unexpectedly long, with 16 of 26 patients alive after a follow-up of 12 months, favoring immune responders.
基于大量转染局部抗原呈递细胞的可能性，开展了一项针对IV期黑色素瘤患者的I期研究，以确定向腹股沟淋巴结反复输注递增剂量的编码酪氨酸酶表位的DNA质粒的实用性、毒性及免疫反应。
每组8例患者，每14天通过泵在96小时内将200微克、400微克或800微克DNA经淋巴结内给药，共进行4个周期。在治疗前、4周后和8周后采集血液进行免疫分析并检测血清中的质粒。在基线和8周后进行扫描和X线检查。
治疗耐受性良好，仅有5例患者出现1-2级毒性。通过96小时将质粒输注到腹股沟淋巴结进行疫苗接种，在107次插管中仅发生1次导管渗漏。血清中检测到质粒的情况在2例患者中罕见且短暂。26例患者中有11例通过肽四聚体分析检测到对酪氨酸酶207-216的免疫反应。未观察到临床反应。该试验中经过大量预处理的患者生存期意外延长，26例患者中有16例在中位随访12个月时仍存活。
将DNA质粒疫苗输注到腹股沟淋巴结是可行的且耐受性良好。观察到对一种新型酪氨酸酶表位的免疫反应。该试验中经过大量预处理的患者总体生存期意外延长，26例患者中有16例在随访12个月后仍存活，免疫反应者更占优势。
