非小细胞肺癌免疫治疗新进展_West China Medical Journal

Authors：

 庞静 ,  彭枫

四川大学华西医院肿瘤中心胸部肿瘤科（成都，610041）;

Corresponding author：

彭枫, Email: pfwork@126.com

Keywords：

非小细胞肺癌; 免疫治疗; 临床研究; 新进展

DOI：

10.7507/1002-0179.20140482

Video：

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Abstract Full text Figures/Tables Video References Cited by

随着肿瘤免疫机制的研究发展，非小细胞肺癌（NSCLC）的免疫治疗逐渐成为研究热点。目前，一些针对NSCLC的抗体或者疫苗，如抗程序性死亡受体1抗体、表皮生长因子疫苗、黑色素瘤相关抗原-A3、BLP25脂质体疫苗，已进行了系列临床研究，并取得了重要的突破。现就此作一综述。

Citation： 庞静, 彭枫. 非小细胞肺癌免疫治疗新进展. West China Medical Journal, 2014, 29(8): 1574-1578. doi: 10.7507/1002-0179.20140482 Copy

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2.	Villaruz LC, Kalyan A, Zarour H, et al. Immunotherapy in lung cancer[J]. Translat Lung Cancer Res, 2014, 3(1):2-14.
3.	Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of Anti-PD-1 antibody in cancer[J]. N Engl J Med, 2012, 366(26):2443-2454.
4.	Borghaei H, Lynch TJ, Naiyer AR, et al. A phase Ⅲ comparative study of nivolumab (anti-PD-1; BMS-936558; ONO-4538) versus docetaxel in patients with previously treated advanced or metastatic squamous cell non-small cell lung cancer (NSCLC)[C]. ASCO Annual Meeting Abstract, 2013, UN:TPS8122.
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7.	Rodriguez PC, Neninger E, García B, et al. Safety, immunogenicity and preliminary efficacy of multiple-site vaccination with an epidermal growth factor (EGF) based cancer vaccine in advanced non small cell lung cancer (NSCLC) patients[J]. J Immune Based Ther Vaccines, 2011, 9:7.
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12.	Taube JM, Anders RA, Young GD, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape[J]. Sci Transl Med, 2012, 4(127):127ra37.
13.	Vansteenkiste J, Zielinski M, Linder A, et al. Final results of a multi-center, double-blind, randomized, placebo-controlled phaseⅡ study to assess the efficacy of MAGE-A3 immunotherapeutic as adjuvant therapy in stageⅠB/Ⅱ non-small cell lung cancer (NSCLC)[J]. J Clin Oncol, 2007, 25(18S):7554.
14.	Vansteenkiste J, Zielinski M, Linder A, et al. Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer:phaseⅡ randomized study results[J]. J Clin Oncol, 2013, 31(19):2396-2403.
15.	Tyagi P, Mirakhur B. MAGRIT:the largest-ever phaseⅢ lung cancer trial aims to establish a novel tumor-specific approach to therapy[J]. Clin Lung Cancer, 2009, 10(5):371-374.
16.	Bafna S, Kaur S, Batra SK. Membrane-bound mucins:the mechanistic basis for alterations in the growth and survival of cancer cells[J]. Oncogene, 2010, 29(20):2893-2904.
17.	Acres B, Limacher JM. MUC1 as a target antigen for cancer immunotherapy[J]. Expert Rev Vaccines, 2005, 4(4):493-502.
18.	Butts C, Murray N, Maksymiuk A, et al. Randomized phaseⅡB trial of BLP25 liposome vaccine in stage ⅢB and Ⅳ non-small-cell lung cancer[J]. J Clin Oncol, 2005, 23(27):6674-6681.
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24.	Nemunaitis J, Nemunaitis M, Senzer N, et al. PhaseⅡ trial of Belagenpumatucel-L, a TGF-beta2 antisense gene modified allogeneic tumor vaccine in advanced non small cell lung cancer (NSCLC) patients[J]. Cancer Gene Ther, 2009, 16(8):620-624.
25.	Kong F, Jirtle RL, Huang DH, et al. Plasma transforming growth factor-beta1 level before radiotherapy correlates with long term outcome of patients with lung carcinoma[J]. Cancer, 1999, 86(9):1712-1719.
26.	Nemunaitis J, Dillman RO, Schwarzenberger PO, et al. Phase Ⅱstudy of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer[J]. J Clin Oncol, 2006, 24(29):4721-4730.
27.	O' brien MR, Saini A, Smith IE, et al. A randomized phase Ⅱ study of SRL172(Mycobacterium vaccae) combined with chemotherapy in patients with advanced inoperable non-small-cell lung cancer and mesothelioma[J]. Br J Cancer, 2000, 83(7):853.
28.	Hirsh V, Paz-Ares L, Boyer M, et al. Randomized phaseⅢ trial of paclitaxel/carboplatin with or without PF-3512676(Toll-like receptor 9 agonist) as first-line treatment for advanced non-small-cell lung cancer[J]. J Clin Oncol, 2011, 29(19):2667-2674.
29.	Hirsh V, Boyer M, Rosell R, et al. Randomized phaseⅢ trial of paclitaxel/carboplatin with or without PF-3512676(toll-like receptor 9 agonist) as first line treatment of advanced non-small cell lung cancer (NSCLC)[C]. J Clin Oncol (Meeting Abstracts), 2008(Suppl 15):8016.

1. Shimanovsky A, Dasanu CA. Updates on immunotherapy in non-small cell lung cancer[J]. Expert Opin Biol Ther, 2014, 14(4):411-418.
2. Villaruz LC, Kalyan A, Zarour H, et al. Immunotherapy in lung cancer[J]. Translat Lung Cancer Res, 2014, 3(1):2-14.
3. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of Anti-PD-1 antibody in cancer[J]. N Engl J Med, 2012, 366(26):2443-2454.
4. Borghaei H, Lynch TJ, Naiyer AR, et al. A phase Ⅲ comparative study of nivolumab (anti-PD-1; BMS-936558; ONO-4538) versus docetaxel in patients with previously treated advanced or metastatic squamous cell non-small cell lung cancer (NSCLC)[C]. ASCO Annual Meeting Abstract, 2013, UN:TPS8122.
5. Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer[J]. N Engl J Med, 2012, 366(26):2455-2465.
6. Spigel DR, Gettinger SN, Horn L, et al. Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)[C]. ASCO Annual Meeting Abstract, 2013, UN:no8008.
7. Rodriguez PC, Neninger E, García B, et al. Safety, immunogenicity and preliminary efficacy of multiple-site vaccination with an epidermal growth factor (EGF) based cancer vaccine in advanced non small cell lung cancer (NSCLC) patients[J]. J Immune Based Ther Vaccines, 2011, 9:7.
8. Neninger Vinageras E, de la Torre A, Osorio Rodríguez M, et al. PhaseⅡ randomized controlled trial of an epidermal growth factor vaccine in advanced non-small-cell lung cancer[J]. J Clin Oncol, 2008, 26(9):1452-1458.
9. Ramos TC, Neninger E, Acosta S, et al. EGF-based cancer vaccine for advanced NSCLC:results from a phaseⅢ trial[C]. ASCO Annual Meeting Abstract, 2012, UN:no2527.
10. Wu YL, Park K, Soo RA, et al. INSPIRE:a phaseⅢ study of the BLP25 liposome vaccine (L-BLP25) in Asian patients with unresectable stageⅢ non-small cell lung cancer[J]. BMC Cancer, 2011, 11(1):430.
11. PhaseⅢ LucanixTM vaccine therapy in advanced non-small-cell lung cancer (NSCLC) Following Front-line Chemotherapy (STOP)[DB/OL]. http://clinicaltrials.gov/show/NCT00676507.
12. Taube JM, Anders RA, Young GD, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape[J]. Sci Transl Med, 2012, 4(127):127ra37.
13. Vansteenkiste J, Zielinski M, Linder A, et al. Final results of a multi-center, double-blind, randomized, placebo-controlled phaseⅡ study to assess the efficacy of MAGE-A3 immunotherapeutic as adjuvant therapy in stageⅠB/Ⅱ non-small cell lung cancer (NSCLC)[J]. J Clin Oncol, 2007, 25(18S):7554.
14. Vansteenkiste J, Zielinski M, Linder A, et al. Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer:phaseⅡ randomized study results[J]. J Clin Oncol, 2013, 31(19):2396-2403.
15. Tyagi P, Mirakhur B. MAGRIT:the largest-ever phaseⅢ lung cancer trial aims to establish a novel tumor-specific approach to therapy[J]. Clin Lung Cancer, 2009, 10(5):371-374.
16. Bafna S, Kaur S, Batra SK. Membrane-bound mucins:the mechanistic basis for alterations in the growth and survival of cancer cells[J]. Oncogene, 2010, 29(20):2893-2904.
17. Acres B, Limacher JM. MUC1 as a target antigen for cancer immunotherapy[J]. Expert Rev Vaccines, 2005, 4(4):493-502.
18. Butts C, Murray N, Maksymiuk A, et al. Randomized phaseⅡB trial of BLP25 liposome vaccine in stage ⅢB and Ⅳ non-small-cell lung cancer[J]. J Clin Oncol, 2005, 23(27):6674-6681.
19. Butts C, Maksymiuk A, Goss G, et al. Updated survival analysis in patients with stage ⅢB or Ⅳ non-small-cell lung cancer receiving BLP25 liposome vaccine (L-BLP25):phaseⅡB randomized, multicenter, open-label trial[J]. J Cancer Res Clin Oncol, 2011, 137(9):1337-1342.
20. Butts C, Socinski MA, Mitchell PL, et al. Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage Ⅲ non-small-cell lung cancer (START):a randomised, double-blind, phase 3 trial[J]. Lancet Oncol, 2014, 15(1):59-68.
21. Quoix E, Ramlau R, Westeel V, et al. Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer:a controlled phase 2B trial[J]. Lancet Oncol, 2011, 12(12):1125-1133.
22. Elisabeth AQ, Nemunaitis JJ, Burzykowski T, et al. TIME:a phaseⅡb/Ⅲ randomized, double-blind, placebo-controlled study comparing first-line therapy with or without TG4010 immunotherapy product in patients with stageⅣ non-small cell lung cancer (NSCLC)[C]. ASCO Annual Meeting Abstract, 2012. UN:TPS7610.
23. Phase Ⅱb/Ⅲ of tg4010 immunotherapy in patients with stage Ⅳ non-small cell lung cancer (time)[DB/OL]. http://www.clinicaltrials.gov/ct2/show/NCT01383148?term=TG4010+TIME&rank=1.
24. Nemunaitis J, Nemunaitis M, Senzer N, et al. PhaseⅡ trial of Belagenpumatucel-L, a TGF-beta2 antisense gene modified allogeneic tumor vaccine in advanced non small cell lung cancer (NSCLC) patients[J]. Cancer Gene Ther, 2009, 16(8):620-624.
25. Kong F, Jirtle RL, Huang DH, et al. Plasma transforming growth factor-beta1 level before radiotherapy correlates with long term outcome of patients with lung carcinoma[J]. Cancer, 1999, 86(9):1712-1719.
26. Nemunaitis J, Dillman RO, Schwarzenberger PO, et al. Phase Ⅱstudy of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer[J]. J Clin Oncol, 2006, 24(29):4721-4730.
27. O' brien MR, Saini A, Smith IE, et al. A randomized phase Ⅱ study of SRL172(Mycobacterium vaccae) combined with chemotherapy in patients with advanced inoperable non-small-cell lung cancer and mesothelioma[J]. Br J Cancer, 2000, 83(7):853.
28. Hirsh V, Paz-Ares L, Boyer M, et al. Randomized phaseⅢ trial of paclitaxel/carboplatin with or without PF-3512676(Toll-like receptor 9 agonist) as first-line treatment for advanced non-small-cell lung cancer[J]. J Clin Oncol, 2011, 29(19):2667-2674.
29. Hirsh V, Boyer M, Rosell R, et al. Randomized phaseⅢ trial of paclitaxel/carboplatin with or without PF-3512676(toll-like receptor 9 agonist) as first line treatment of advanced non-small cell lung cancer (NSCLC)[C]. J Clin Oncol (Meeting Abstracts), 2008(Suppl 15):8016.

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非小细胞肺癌免疫治疗新进展

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