TSA-DC-CTL细胞免疫治疗联合PD-L1抗体治疗高龄晚期结肠癌1例报道并文献复习
|
摘要
目的报道1例肿瘤特异性抗原(TSA)刺激诱导树突状细胞(DC)及细胞毒性T淋巴细胞(CTL过继治疗联合程序性死亡配体1(PD-L1)抗体治疗高龄晚期结肠癌患者。方法 2018年2月笔者所在医院对1例90岁高龄女性患者因"回盲部癌伴梗阻"行剖腹探查、回盲部切除、小肠部分切除、末端回肠造瘘、腹膜活检术,肿瘤广泛转移,患者基础条件差,术后无法耐受常规治疗。经与患者家属充分沟通知情同意及解放军总医院伦理委员会批准,于术后4个月开始行4次TSA-DC细胞皮内多点注射,4次TSA-CTL细胞静脉滴注,2次TSA-CTL细胞腹腔注入,1次PD-L1抗体1 200 mg静脉滴注。结果行TSA-DC-CTL联合PD-L1治疗后7 d(治疗中期),患者的KPS评分升至80分(治疗前40分),外周血循环肿瘤细胞计数降至7个/3.2 mL(治疗前16个/3.2 mL),肿瘤标志物CA125降至155.5 u/mL(治疗前224.4 u/mL),治疗过程中未见相关不良反应。行TSA-DC-CTL联合PD-L1治疗后36 d患者突然出现血压和血氧饱和度下降,给与升压、兴奋呼吸等治疗,情况好转,因家属要求患者自动出院。结论 TSA-DC-CTL细胞免疫治疗联合PD-L1治疗本例高龄患者安全可行,能在一定程度上改善患者生活质量及部分生物学指标,但TSA-DC-CTL联合PD-L1抗体的安全性及近远期疗效有待进一步研究论证。
引文
1 Bray F,Ferlay J,Soerjomataram I,et al. Global cancer statistics2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin,2018,68(6):394-424.
2 Kemeny NE.Treatment of metastatic colon cancer:"the times they are A-changing".J Clin Oncol,2013,31(16):1913-1916.
3王广伟,顾元龙,胡森焱.人热休克蛋白70-肽复合物/树突状细胞对肝癌的免疫治疗效果研究.中国普外基础与临床杂志,2017,24(2):222-227.
4邹一丰,吴小剑,兰平.结直肠癌免疫治疗.中国普外基础与临床杂志,2006,13(3):358-361.
5 Gopal S.Moonshot to Malawi.N Engl J Med,2016,374(17):1604-1605.
6 Cohen RL,Settleman J. From cancer genomics to precision oncology-tissue's still an issue.Cell,2014,157(7):1509-1514.
7 Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy.Science,2013,342(6165):1432-1433.
8 de Kock I,Mirhosseini M,Lau F,et al. Conversion of Karnofsky Performance Status(KPS)and Eastern Cooperative Oncology Group Performance Status(ECOG)to Palliative Performance Scale(PPS),and the interchangeability of PPS and KPS in prognostic tools. J Palliat Care,2013,29(3):163-169.
9 Rosenberg SA,Restifo NP.Adoptive cell transfer as personalized immunotherapy for human cancer.Science,2015,348(6230):62-68.
10 Robbins PF,Lu YC,El-Gamil M,et al. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells.Nat Med,2013,19(6):747-752.
11 Tran E,Turcotte S,Gros A,et al. Cancer immunotherapy based on mutation-specific CD4 T cells in a patient with epithelial cancer.Science,2014,344(6184):641-645.
12钱其军,吴孟超.肿瘤精准细胞免疫治疗:梦想照进现实.中国肿瘤生物治疗杂志,2015,22(2):151-158.
13 Keir ME,Butte MJ,Freeman GJ,et al. PD-1 and its ligands in tolerance and immunity.Annu Rev Immunol,2008,26:677-704.
14 Chakravarti N,Prieto VG.Predictive factors of activity of antiprogrammed death-1/programmed death ligand-1 drugs:immunohistochemistry analysis.Transl Lung Cancer Res,2015,4(6):743-751.
15 Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, et al.Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2.J Exp Med,2012,209(6):1201-1217.
16 Motzer RJ,Escudier B,Mcdermott DF,et al.Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma.N Engl J Med,2015,373(19):1803-1813.
17 Schachter J,Ribas A,Long GV,et al. Pembrolizumab versus ipilimumab for advanced melanoma:final overall survival results of a multicentre, randomised, open-label phase 3 study(KEYNOTE-006).Lancet,2017,390(10105):1853-1862.
18 Ramos-Esquivel A,van der Laat A,Rojas-Vigott R,et al. Anti-PD-1/anti-PD-L1 immunotherapy versus docetaxel for previously treated advanced non-small cell lung cancer:a systematic review and meta-analysis of randomised clinical trials.ESMO Open,2017,2(3):e000236.
2 Kemeny NE.Treatment of metastatic colon cancer:"the times they are A-changing".J Clin Oncol,2013,31(16):1913-1916.
3王广伟,顾元龙,胡森焱.人热休克蛋白70-肽复合物/树突状细胞对肝癌的免疫治疗效果研究.中国普外基础与临床杂志,2017,24(2):222-227.
4邹一丰,吴小剑,兰平.结直肠癌免疫治疗.中国普外基础与临床杂志,2006,13(3):358-361.
5 Gopal S.Moonshot to Malawi.N Engl J Med,2016,374(17):1604-1605.
6 Cohen RL,Settleman J. From cancer genomics to precision oncology-tissue's still an issue.Cell,2014,157(7):1509-1514.
7 Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy.Science,2013,342(6165):1432-1433.
8 de Kock I,Mirhosseini M,Lau F,et al. Conversion of Karnofsky Performance Status(KPS)and Eastern Cooperative Oncology Group Performance Status(ECOG)to Palliative Performance Scale(PPS),and the interchangeability of PPS and KPS in prognostic tools. J Palliat Care,2013,29(3):163-169.
9 Rosenberg SA,Restifo NP.Adoptive cell transfer as personalized immunotherapy for human cancer.Science,2015,348(6230):62-68.
10 Robbins PF,Lu YC,El-Gamil M,et al. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells.Nat Med,2013,19(6):747-752.
11 Tran E,Turcotte S,Gros A,et al. Cancer immunotherapy based on mutation-specific CD4 T cells in a patient with epithelial cancer.Science,2014,344(6184):641-645.
12钱其军,吴孟超.肿瘤精准细胞免疫治疗:梦想照进现实.中国肿瘤生物治疗杂志,2015,22(2):151-158.
13 Keir ME,Butte MJ,Freeman GJ,et al. PD-1 and its ligands in tolerance and immunity.Annu Rev Immunol,2008,26:677-704.
14 Chakravarti N,Prieto VG.Predictive factors of activity of antiprogrammed death-1/programmed death ligand-1 drugs:immunohistochemistry analysis.Transl Lung Cancer Res,2015,4(6):743-751.
15 Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, et al.Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2.J Exp Med,2012,209(6):1201-1217.
16 Motzer RJ,Escudier B,Mcdermott DF,et al.Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma.N Engl J Med,2015,373(19):1803-1813.
17 Schachter J,Ribas A,Long GV,et al. Pembrolizumab versus ipilimumab for advanced melanoma:final overall survival results of a multicentre, randomised, open-label phase 3 study(KEYNOTE-006).Lancet,2017,390(10105):1853-1862.
18 Ramos-Esquivel A,van der Laat A,Rojas-Vigott R,et al. Anti-PD-1/anti-PD-L1 immunotherapy versus docetaxel for previously treated advanced non-small cell lung cancer:a systematic review and meta-analysis of randomised clinical trials.ESMO Open,2017,2(3):e000236.