PDF(Pubmed)
Abstract：
UNASSIGNED: In the era of immune checkpoint blockade, the role of cancer vaccines in immune priming has provided additional potential for therapeutic improvements. Prior studies have demonstrated delayed type hypersensitivity and anti-tumor immunity with vaccines engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF). The safety, efficacy and anti-tumor immunity of GM-CSF secreting vaccine in patients with previously treated stage III or IV melanoma needs further investigation.
UNASSIGNED: In this phase II trial, excised lymph node metastases were processed to single cells, transduced with an adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines were composed of 1x106, 4x106, or 1x107 tumor cells, and were injected intradermally and subcutaneously at weekly and biweekly intervals. The primary endpoints were feasibility of producing vaccine in stage III patients and determining the proportion of patients alive at two years in stage IV patients.
UNASSIGNED: GM-CSF vaccine was successfully developed and administered in all 61 patients. Toxicities were restricted to grade 1-2 local skin reactions. The median OS for stage III patients (n = 20) was 71.1 (95% CI, 43.7 to NR) months and 14.9 (95%CI, 12.1 to 39.7) months for stage IV patients. The median PFS in stage III patients was 50.7 (95%CI, 36.3 to NR) months and 4.1 (95% CI, 3.0-6.3) months in stage IV patients. In the overall population, the disease control rate was 39.3% (95%CI, 27.1 to 52.7%). In stage III patients, higher pre-treatment plasma cytokine levels of MMP-1, TRAIL, CXCL-11, CXCL-13 were associated with improved PFS (p<0.05 for all). An increase in post-vaccination levels of IL-15 and TRAIL for stage III patients was associated with improved PFS (p=0.03 for both). Similarly, an increase in post-vaccination IL-16 level for stage IV patients was associated with improved PFS (p=0.02) and clinical benefit.
UNASSIGNED: Vaccination with autologous melanoma cells secreting GM-CSF augments antitumor immunity in stage III and IV patients with melanoma, is safe, and demonstrates disease control. Luminex data suggests that changes in inflammatory cytokines and immune cell infiltration promote tumor antigen presentation and subsequent tumor cell destruction. Additional investigation to administer this vaccine in combination with immune checkpoint inhibitors is needed.
UNASSIGNED: In this phase II trial, excised lymph node metastases were processed to single cells, transduced with an adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines were composed of 1x106, 4x106, or 1x107 tumor cells, and were injected intradermally and subcutaneously at weekly and biweekly intervals. The primary endpoints were feasibility of producing vaccine in stage III patients and determining the proportion of patients alive at two years in stage IV patients.
UNASSIGNED: GM-CSF vaccine was successfully developed and administered in all 61 patients. Toxicities were restricted to grade 1-2 local skin reactions. The median OS for stage III patients (n = 20) was 71.1 (95% CI, 43.7 to NR) months and 14.9 (95%CI, 12.1 to 39.7) months for stage IV patients. The median PFS in stage III patients was 50.7 (95%CI, 36.3 to NR) months and 4.1 (95% CI, 3.0-6.3) months in stage IV patients. In the overall population, the disease control rate was 39.3% (95%CI, 27.1 to 52.7%). In stage III patients, higher pre-treatment plasma cytokine levels of MMP-1, TRAIL, CXCL-11, CXCL-13 were associated with improved PFS (p<0.05 for all). An increase in post-vaccination levels of IL-15 and TRAIL for stage III patients was associated with improved PFS (p=0.03 for both). Similarly, an increase in post-vaccination IL-16 level for stage IV patients was associated with improved PFS (p=0.02) and clinical benefit.
UNASSIGNED: Vaccination with autologous melanoma cells secreting GM-CSF augments antitumor immunity in stage III and IV patients with melanoma, is safe, and demonstrates disease control. Luminex data suggests that changes in inflammatory cytokines and immune cell infiltration promote tumor antigen presentation and subsequent tumor cell destruction. Additional investigation to administer this vaccine in combination with immune checkpoint inhibitors is needed.
摘要：
■在免疫检查点封锁的时代,癌症疫苗在免疫启动中的作用为治疗改进提供了额外的潜力.先前的研究已经证明了用工程化以分泌粒细胞-巨噬细胞集落刺激因子(GM-CSF)的疫苗的迟发型超敏反应和抗肿瘤免疫。安全,GM-CSF分泌疫苗在既往治疗过的III或IV期黑色素瘤患者中的疗效和抗肿瘤免疫力需要进一步研究.
■在此II期试验中，切除的淋巴结转移被处理为单细胞，用编码GM-CSF的腺病毒载体转导，辐照,并冷冻保存。个体疫苗由1x106、4x106或1x107个肿瘤细胞组成，并以每周和每两周的间隔进行皮内和皮下注射。主要终点是在III期患者中生产疫苗的可行性，并确定IV期患者中两年存活的患者比例。
■成功开发了GM-CSF疫苗，并在所有61名患者中使用。毒性限于1-2级局部皮肤反应。III期患者（n=20）的中位OS为71.1（95％CI，43.7至NR）个月，IV期患者为14.9（95CI，12.1至39.7）个月。III期患者的中位PFS为50.7（95CI，36.3至NR）个月，IV期患者为4.1（95％CI，3.0-6.3）个月。在总人口中,疾病控制率为39.3%(95CI,27.1～52.7%)。在III期患者中，较高的治疗前血浆细胞因子水平的MMP-1，TRAIL，CXCL-11、CXCL-13与改善的PFS相关(均p<0.05)。III期患者的IL-15和TRAIL疫苗接种后水平的增加与改善的PFS相关(两者的p=0.03)。同样，IV期患者的疫苗接种后IL-16水平升高与PFS改善(p=0.02)和临床获益相关.
■接种分泌GM-CSF的自体黑色素瘤细胞可增强III期和IV期黑色素瘤患者的抗肿瘤免疫力，是安全的,并证明疾病控制。Luminex数据表明，炎症细胞因子和免疫细胞浸润的变化促进了肿瘤抗原呈递和随后的肿瘤细胞破坏。需要进行额外的研究以将该疫苗与免疫检查点抑制剂组合施用。
■在此II期试验中，切除的淋巴结转移被处理为单细胞，用编码GM-CSF的腺病毒载体转导，辐照,并冷冻保存。个体疫苗由1x106、4x106或1x107个肿瘤细胞组成，并以每周和每两周的间隔进行皮内和皮下注射。主要终点是在III期患者中生产疫苗的可行性，并确定IV期患者中两年存活的患者比例。
■成功开发了GM-CSF疫苗，并在所有61名患者中使用。毒性限于1-2级局部皮肤反应。III期患者（n=20）的中位OS为71.1（95％CI，43.7至NR）个月，IV期患者为14.9（95CI，12.1至39.7）个月。III期患者的中位PFS为50.7（95CI，36.3至NR）个月，IV期患者为4.1（95％CI，3.0-6.3）个月。在总人口中,疾病控制率为39.3%(95CI,27.1～52.7%)。在III期患者中，较高的治疗前血浆细胞因子水平的MMP-1，TRAIL，CXCL-11、CXCL-13与改善的PFS相关(均p<0.05)。III期患者的IL-15和TRAIL疫苗接种后水平的增加与改善的PFS相关(两者的p=0.03)。同样，IV期患者的疫苗接种后IL-16水平升高与PFS改善(p=0.02)和临床获益相关.
■接种分泌GM-CSF的自体黑色素瘤细胞可增强III期和IV期黑色素瘤患者的抗肿瘤免疫力，是安全的,并证明疾病控制。Luminex数据表明，炎症细胞因子和免疫细胞浸润的变化促进了肿瘤抗原呈递和随后的肿瘤细胞破坏。需要进行额外的研究以将该疫苗与免疫检查点抑制剂组合施用。
