Immunotherapy in Lung Cancer: “B7-Bombers” and Other New Developments

Ben C. Creelan; Scott J. Antonia

doi:10.1055/s-0033-1358551

Seminars in Respiratory and Critical Care Medicine, Inhaltsverzeichnis

Semin Respir Crit Care Med 2013; 34(06): 810-821
DOI: 10.1055/s-0033-1358551

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Immunotherapy in Lung Cancer: “B7-Bombers” and Other New Developments

Ben C. Creelan

¹Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida

,

Scott J. Antonia

¹Department of Thoracic Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida

› Institutsangaben

Abstract

Several recent immunotherapy agents have exhibited exceptional activity, and their eventual approval for use in lung cancer appears plausible. The immune checkpoint proteins, such as the B7 superfamily, are becoming increasingly relevant targets for therapeutic inhibition. Tumor vaccines hold the potential to deliver durable responses that are specific for tumor antigen, with favorable adverse effect profiles. Several vaccine trials are accruing more patients than any previous lung cancer trials and are designed to select a specific population based on a predefined, scientifically justified biomarker. These emerging immune treatments may hold great potential for the systemic treatment of lung cancers.

Keywords

immunoediting - driver immunosuppressors - programmed cell death-1 (PD-1) - membrane-associated glycoprotein (MUC-1) - cytotoxic T-lymphocyte antigen-4 (CTLA-4)

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References
1 Matsushita H, Vesely MD, Koboldt DC , et al. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature 2012; 482 (7385) 400-404
2 Derniame S, Vignaud JM, Faure GC, Béné MC. Alteration of the immunological synapse in lung cancer: a microenvironmental approach. Clin Exp Immunol 2008; 154 (1) 48-55
3 Kida H, Ihara S, Kumanogoh A. Involvement of STAT3 in immune evasion during lung tumorigenesis. OncoImmunology 2013; 2 (1) e22653
4 Schneider T, Hoffmann H, Dienemann H , et al. Non-small cell lung cancer induces an immunosuppressive phenotype of dendritic cells in tumor microenvironment by upregulating B7-H3. J Thorac Oncol 2011; 6 (7) 1162-1168
5 Sterlacci W, Wolf D, Savic S , et al. High transforming growth factor . β expression represents an important prognostic parameter for surgically resected non-small cell lung cancer. Hum Pathol 2012; 43 (3) 339-349
6 Salmon H, Donnadieu E. Within tumors, interactions between T cells and tumor cells are impeded by the extracellular matrix. OncoImmunology 2012; 1 (6) 992-994
7 Salmon H, Franciszkiewicz K, Damotte D , et al. Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors. J Clin Invest 2012; 122 (3) 899-910
8 Ramnath N, Tan D, Li Q , et al. Is downregulation of MHC class I antigen expression in human non-small cell lung cancer associated with prolonged survival?. Cancer Immunol Immunother 2006; 55 (8) 891-899
9 Lin A, Zhu CC, Chen HX , et al. Clinical relevance and functional implications for human leucocyte antigen-g expression in non-small-cell lung cancer. J Cell Mol Med 2010; 14 (9) 2318-2329
10 Hanagiri T, Shigematsu Y, Kuroda K , et al. Prognostic implications of human leukocyte antigen class I expression in patients who underwent surgical resection for non–small-cell lung cancer. J Surg Res 2013; 181 (2) e57-e63
11 Woo EY, Yeh H, Chu CS , et al. Cutting edge: regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J Immunol 2002; 168 (9) 4272-4276
12 Lesokhin AM, Hohl TM, Kitano S , et al. Monocytic CCR2(+) myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment. Cancer Res 2012; 72 (4) 876-886
13 Nagaraj S, Youn J-I, Gabrilovich DI. Reciprocal relationship between myeloid-derived suppressor cells and T cells. J Immunol 2013; 191 (1) 17-23
14 Kelly RJ, Giaccone G. Lung cancer vaccines. Cancer J 2011; 17 (5) 302-308
15 Erfani N, Mehrabadi SM, Ghayumi MA , et al. Increase of regulatory T cells in metastatic stage and CTLA-4 over expression in lymphocytes of patients with non-small cell lung cancer (NSCLC). Lung Cancer 2012; 77 (2) 306-311
16 Li L, Chao QG, Ping LZ , et al. The prevalence of FOXP3+ regulatory T-cells in peripheral blood of patients with NSCLC. Cancer Biother Radiopharm 2009; 24 (3) 357-367
17 Zatloukal P, Heo D, Park K , et al. Randomized phase II clinical trial comparing tremelimumab (CP-675,206) with best supportive care (BSC) following first-line platinum-based therapy in patients (pts) with advanced non-small cell lung cancer (NSCLC). J Clin Oncol 2009; 27 (15S):abstract 8071
18 Lynch TJ, Bondarenko I, Luft A , et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol 2012; 30 (17) 2046-2054
19 Wolchok JD, Hoos A, O'Day S , et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 2009; 15 (23) 7412-7420
20 Genova C, Rijavec E, Barletta G , et al. Ipilimumab (MDX-010) in the treatment of non-small cell lung cancer. Expert Opin Biol Ther 2012; 12 (7) 939-948
21 Reck M, Bondarenko I, Luft A , et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol 2013; 24 (1) 75-83
22 Liu H, Zhang T, Ye J , et al. Tumor-infiltrating lymphocytes predict response to chemotherapy in patients with advance non-small cell lung cancer. Cancer Immunol Immunother 2012; 61 (10) 1849-1856
23 Reck M. What future opportunities may immuno-oncology provide for improving the treatment of patients with lung cancer?. Ann Oncol 2012; 23 (Suppl. 08) viii28-34
24 Agata Y, Kawasaki A, Nishimura H , et al. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int Immunol 1996; 8 (5) 765-772
25 Sauce D, Almeida JR, Larsen M , et al. PD-1 expression on human CD8 T cells depends on both state of differentiation and activation status. AIDS 2007; 21 (15) 2005-2013
26 Liang SC, Latchman YE, Buhlmann JE , et al. Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses. Eur J Immunol 2003; 33 (10) 2706-2716
27 Konishi J, Yamazaki K, Azuma M, Kinoshita I, Dosaka-Akita H, Nishimura M. B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clin Cancer Res 2004; 10 (15) 5094-5100
28 Sasaki H, Suzuki A, Shitara M , et al. PD-L1 gene expression in Japanese lung cancer patients. Biomedical Reports 2013; 1 (1) 93-96
29 Velcheti V, Rimm DL, Schalper KA. Sarcomatoid lung carcinomas show high levels of programmed death ligand-1 (PD-L1). J Thorac Oncol 2013; 8 (6) 803-805
30 Boland JM, Kwon ED, Harrington SM , et al. Tumor B7-H1 and B7-H3 Expression in Squamous Cell Carcinoma of the Lung. Clin Lung Cancer 2013; 14 (2) 157-163
31 Mu C-Y, Huang J-A, Chen Y, Chen C, Zhang X-G. High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation. Med Oncol 2011; 28 (3) 682-688
32 Chen YB, Mu CY, Chen C, Huang JA. Association between single nucleotide polymorphism of PD-L1 gene and non-small cell lung cancer susceptibility in a Chinese population. Asia Pac J Clin Oncol 2012; Nov 21. doi:10.1111/ajco.12037. [Epub ahead of print]
33 Chen C, Shen Y, Qu QX, Chen XQ, Zhang XG, Huang JA. Induced expression of B7-H3 on the lung cancer cells and macrophages suppresses T-cell mediating anti-tumor immune response. Exp Cell Res 2013; 319 (1) 96-102
34 Zhang G, Xu Y, Lu X , et al. Diagnosis value of serum B7-H3 expression in non-small cell lung cancer. Lung Cancer 2009; 66 (2) 245-249
35 Sun Y, Wang Y, Zhao J , et al. B7-H3 and B7-H4 expression in non-small-cell lung cancer. Lung Cancer 2006; 53 (2) 143-151
36 Zhou YH, Chen YJ, Ma ZY , et al. 4IgB7-H3 is the major isoform expressed on immunocytes as well as malignant cells. Tissue Antigens 2007; 70 (2) 96-104
37 Zhang Y, Huang S, Gong D, Qin Y, Shen Q. Programmed death-1 upregulation is correlated with dysfunction of tumor-infiltrating CD8+ T lymphocytes in human non-small cell lung cancer. Cell Mol Immunol 2010; 7 (5) 389-395
38 Topalian SL, Brahmer JR, McDermott DF , et al. Survival and Long-Term Safety in Cancer Patients Receiving the PD-1 Antibody Nivolumab. N Engl J Med 2013; ; In press
39 Rizvi N. A phase I study of nivolumab (anti-PD-1; BMS-936558, ONO-4538) plus platinum-based doublet chemotherapy (PT-doublet) in chemotherapy-naive non-small cell lung cancer (NSCLC) patients (pts). J Clin Oncol 2013; 31 (Suppl;):abstract 8072
40 Wolchok JD, Kluger H, Callahan MK , et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013; 369 (2) 122-133
41 Lipson EJ, Sharfman WH, Drake CG , et al. Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody. Clin Cancer Res 2013; 19 (2) 462-468
42 Patnaik A, Kang SP, Tolcher AW , et al. Phase I study of MK-3475 (anti-PD-1 monoclonal antibody) in patients with advanced solid tumors. J Clin Oncol 2012; 30 (15S):abstract 2512
43 Hamid O, Robert C, Daud A , et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013; 369 (2) 134-144
44 Beck A, Wurch T, Reichert JM. Sixth Annual European Antibody Congress 2010: November 29–December 1, 2010; Geneva, Switzerland. MAbs: Austin, TX: Landes Bioscience: 2011: 111-132
45 Mkrtichyan M, Najjar YG, Raulfs EC , et al. Anti-PD-1 synergizes with cyclophosphamide to induce potent anti-tumor vaccine effects through novel mechanisms. Eur J Immunol 2011; 41 (10) 2977-2986
46 Brahmer JR, Tykodi SS, Chow LQ , et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012; 366 (26) 2455-2465
47 Herbst R. A study of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic tumors. J Clin Oncol 2013; 31 (15S):abstract 3000
48 Powderly JD. Biomarkers and associations with the clinical activity of PD-L1 blockade in a MPDL3280A study. J Clin Oncol 2013; 31 (15S):abstract 3001
49 Mühlbauer M, Fleck M, Schütz C , et al. PD-L1 is induced in hepatocytes by viral infection and by interferon-. α and -γ and mediates T cell apoptosis. J Hepatol 2006; 45 (4) 520-528
50 Freidin MB, Bhudia N, Lim E, Nicholson AG, Cookson WO, Moffatt MF. Impact of collection and storage of lung tumor tissue on whole genome expression profiling. J Mol Diagn 2012; 14 (2) 140-148
51 Mkrtichyan MNY, Najjar YG, Raulfs EC , et al. B7-DC-Ig enhances vaccine effect by a novel mechanism dependent on PD-1 expression level on T cell subsets. J Immunol 2012; 189 (5) 2338-2347
52 Smothers F, Hoos A, Langermann S , et al. AMP-224, a fusion protein that targets PD-1. Ann Oncol 2013; 24 (Suppl. 01) i7-i17
53 Infante J. Clinical and pharmacodynamic (PD) results of a phase I trial with AMP-224 (B7-DC Fc) that binds to the PD-1 receptor. J Clin Oncol 2013; 31 (15S):abstract 3044
54 Jacobs R, Hintzen G, Kemper A , et al. CD56bright cells differ in their KIR repertoire and cytotoxic features from CD56dim NK cells. Eur J Immunol 2001; 31 (10) 3121-3127
55 Carrega P, Morandi B, Costa R , et al. Natural killer cells infiltrating human nonsmall-cell lung cancer are enriched in CD56 bright CD16(-) cells and display an impaired capability to kill tumor cells. Cancer 2008; 112 (4) 863-875
56 Al Omar S, Middleton D, Marshall E , et al. Associations between genes for killer immunoglobulin-like receptors and their ligands in patients with solid tumors. Hum Immunol 2010; 71 (10) 976-981
57 Al Omar SY, Marshall E, Middleton D, Christmas SE. Increased numbers but functional defects of CD56+CD3+ cells in lung cancer. Int Immunol 2012; 24 (7) 409-415
58 Al Omar SY, Marshall E, Middleton D, Christmas SE. Increased killer immunoglobulin-like receptor expression and functional defects in natural killer cells in lung cancer. Immunology 2011; 133 (1) 94-104
59 Dorothée G, Echchakir H, Le Maux Chansac B , et al. Functional and molecular characterization of a KIR3DL2/p140 expressing tumor-specific cytotoxic T lymphocyte clone infiltrating a human lung carcinoma. Oncogene 2003; 22 (46) 7192-7198
60 Wiśniewski A, Jankowska R, Passowicz-Muszyńska E , et al. KIR2DL2/S2 and HLA-C C1C1 genotype is associated with better response to treatment and prolonged survival of patients with non-small cell lung cancer in a Polish Caucasian population. Hum Immunol 2012; 73 (9) 927-931
61 Sanborn R. A phase I dose-escalation and cohort expansion study of lirilumab (anti-KIR; BMS-986015) administered in combination with nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients (Pts) with advanced refractory solid tumors. J Clin Oncol 2013; 31 (15S):abstract TPS3110
62 Rizvi NA, Infante JR, Gibney GT , et al. A Phase I Study of Lirilumab (BMS-986015), an Anti-KIR Monoclonal Antibody, Administered with Ipilimumab, an Anti-CTLA-4 Monoclonal Antibody, in Patients with Select Advanced Solid Tumors. J Clin Oncol 2013; 31 (15S):abstract TPS3106
63 Sznol M, Hodi F, Margolin K , et al. Phase I study of BMS-663513, a fully human anti-CD137 agonist monoclonal antibody, in patients (pts) with advanced cancer (CA). J Clin Oncol 2008; 26 (15S):abstract 3007
64 Matsuzaki J, Gnjatic S, Mhawech-Fauceglia P , et al. Tumor-infiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proc Natl Acad Sci U S A 2010; 107 (17) 7875-7880
65 Okazaki T, Okazaki IM, Wang J , et al. PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice. J Exp Med 2011; 208 (2) 395-407
66 Woo S-R, Turnis ME, Goldberg MV , et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res 2012; 72 (4) 917-927
67 Brunsvig PF, Kyte JA, Kersten C , et al. Telomerase peptide vaccination in NSCLC: a phase II trial in stage III patients vaccinated after chemoradiotherapy and an 8-year update on a phase I/II trial. Clin Cancer Res 2011; 17 (21) 6847-6857
68 Dalyot-Herman N, Bathe OF, Malek TR. Reversal of CD8+ T cell ignorance and induction of anti-tumor immunity by peptide-pulsed APC. J Immunol 2000; 165 (12) 6731-6737
69 Boczkowski D, Nair SK, Snyder D, Gilboa E. Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J Exp Med 1996; 184 (2) 465-472
70 Chiodoni C, Paglia P, Stoppacciaro A, Rodolfo M, Parenza M, Colombo MP. Dendritic cells infiltrating tumors cotransduced with granulocyte/macrophage colony-stimulating factor (GM-CSF) and CD40 ligand genes take up and present endogenous tumor-associated antigens, and prime naive mice for a cytotoxic T lymphocyte response. J Exp Med 1999; 190 (1) 125-133
71 Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med 1994; 179 (4) 1109-1118
72 Salgia R, Lynch T, Skarin A , et al. Vaccination with irradiated autologous tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor augments antitumor immunity in some patients with metastatic non-small-cell lung carcinoma. J Clin Oncol 2003; 21 (4) 624-630
73 Nemunaitis J, Vorhies JS, Pappen B, Senzer N. 10-year follow-up of gene-modified adenoviral-based therapy in 146 non-small-cell lung cancer patients. Cancer Gene Ther 2007; 14 (8) 762-763
74 Nemunaitis J, Sterman D, Jablons D , et al. Granulocyte-macrophage colony-stimulating factor gene-modified autologous tumor vaccines in non-small-cell lung cancer. J Natl Cancer Inst 2004; 96 (4) 326-331
75 Borrello I, Sotomayor EM, Cooke S, Levitsky HI. A universal granulocyte-macrophage colony-stimulating factor-producing bystander cell line for use in the formulation of autologous tumor cell-based vaccines. Hum Gene Ther 1999; 10 (12) 1983-1991
76 Nemunaitis J, Jahan T, Ross H , et al. Phase 1/2 trial of autologous tumor mixed with an allogeneic GVAX vaccine in advanced-stage non-small-cell lung cancer. Cancer Gene Ther 2006; 13 (6) 555-562
77 Morales JK, Kmieciak M, Knutson KL, Bear HD, Manjili MH. GM-CSF is one of the main breast tumor-derived soluble factors involved in the differentiation of CD11b-Gr1- bone marrow progenitor cells into myeloid-derived suppressor cells. Breast Cancer Res Treat 2010; 123 (1) 39-49
78 Serafini P, Carbley R, Noonan KA, Tan G, Bronte V, Borrello I. High-dose granulocyte-macrophage colony-stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells. Cancer Res 2004; 64 (17) 6337-6343
79 Morse MA, Hobeika AC, Osada T , et al. Depletion of human regulatory T cells specifically enhances antigen-specific immune responses to cancer vaccines. Blood 2008; 112 (3) 610-618
80 Nicholaou T, Ebert LM, Davis ID , et al. Regulatory T-cell-mediated attenuation of T-cell responses to the NY-ESO-1 ISCOMATRIX vaccine in patients with advanced malignant melanoma. Clin Cancer Res 2009; 15 (6) 2166-2173
81 Antonia SJ, Mule JJ. Chemokine gene-modified cells for cancer immunotherapy. United States Patent Application 20130251752, Publication Date: Sept 2013. Available at: http://www.freepatentsonline.com/y2013/0251752.html
82 Wroblewski JM, Bixby DL, Borowski C, Yannelli JR. Characterization of human non-small cell lung cancer (NSCLC) cell lines for expression of MHC, co-stimulatory molecules and tumor-associated antigens. Lung Cancer 2001; 33 (2-3) 181-194
83 Michael A, Ball G, Quatan N , et al. Delayed disease progression after allogeneic cell vaccination in hormone-resistant prostate cancer and correlation with immunologic variables. Clin Cancer Res 2005; 11 (12) 4469-4478
84 Bercovici N, Haicheur N, Massicard S , et al. Analysis and characterization of antitumor T-cell response after administration of dendritic cells loaded with allogeneic tumor lysate to metastatic melanoma patients. J Immunother 2008; 31 (1) 101-112
85 Cella M, Scheidegger D, Palmer-Lehmann K, Lane P, Lanzavecchia A, Alber G. Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J Exp Med 1996; 184 (2) 747-752
86 Dessureault S, Alsarraj M, McCarthy S , et al. A GM-CSF/CD40L producing cell augments anti-tumor T cell responses. J Surg Res 2005; 125 (2) 173-181
87 Dessureault S, Noyes D, Lee D , et al. A phase-I trial using a universal GM-CSF-producing and CD40L-expressing bystander cell line (GM.CD40L) in the formulation of autologous tumor cell-based vaccines for cancer patients with stage IV disease. Ann Surg Oncol 2007; 14 (2) 869-884
88 Yousefieh N, Hahto SM, Stephens AL, Ciavarra RP. Regulated expression of CCL21 in the prostate tumor microenvironment inhibits tumor growth and metastasis in an orthotopic model of prostate cancer. Cancer Microenviron 2009; 2 (1) 59-67
89 Hall RD, Gray JE, Chiappori AA. Beyond the standard of care: a review of novel immunotherapy trials for the treatment of lung cancer. Cancer Control 2013; 20 (1) 22-31
90 Nemunaitis J, Dillman RO, Schwarzenberger PO , et al. Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer. J Clin Oncol 2006; 24 (29) 4721-4730
91 Derynck R, Akhurst RJ, Balmain A. TGF-. β signaling in tumor suppression and cancer progression. Nat Genet 2001; 29 (2) 117-129
92 Weiss A, Attisano L. The TGFbeta superfamily signaling pathway. Wiley Interdiscip Rev Dev Biol 2013; 2 (1) 47-63
93 Saji H, Nakamura H, Awut I , et al. Significance of expression of TGF-beta in pulmonary metastasis in non-small cell lung cancer tissues. Ann Thorac Cardiovasc Surg 2003; 9 (5) 295-300
94 Vujaskovic Z, Groen HJ. TGF-beta, radiation-induced pulmonary injury and lung cancer. Int J Radiat Biol 2000; 76 (4) 511-516
95 Nemunaitis J, Nemunaitis M, Senzer N , et al. Phase II trial of Belagenpumatucel-L, a TGF-. β2 antisense gene modified allogeneic tumor vaccine in advanced non small cell lung cancer (NSCLC) patients. Cancer Gene Ther 2009; 16 (8) 620-624
96 INSPIRE. Is the Lucanix Phase 3 Trial Over? 2012. http://www.inspire.com/groups/lung-cancer-survivors/discussion/is-lucanix-phase-3-trial-over/ . Accessed June 2013
97 Fakhrai H. ClinicalTrials.gov. Phase III study of Lucanix (belagenpumatucel-L) in advanced non-small cell lung cancer. NCT 00676507. http://clinicaltrials.gov/show/NCT00676507 . Accessed July 2013
98 Finn OJ, Jerome KR, Henderson RA , et al. MUC-1 epithelial tumor mucin-based immunity and cancer vaccines. Immunol Rev 1995; 145 (1) 61-89
99 Bansal AS, Bruce J, Devine PL, Scells B, Zimmermann PV. Serum cytokines and tumour markers in patients with non-small cell carcinoma of the lung. Dis Markers 1997; 13 (3) 195-199
100 Lloyd KO, Burchell J, Kudryashov V, Yin BW, Taylor-Papadimitriou J. Comparison of O-linked carbohydrate chains in MUC-1 mucin from normal breast epithelial cell lines and breast carcinoma cell lines: demonstration of simpler and fewer glycan chains in tumor cells. J Biol Chem 1996; 271 (52) 33325-33334
101 Dahiya R, Kwak K-S, Byrd JC, Ho S, Yoon WH, Kim YS. Mucin synthesis and secretion in various human epithelial cancer cell lines that express the MUC-1 mucin gene. Cancer Res 1993; 53 (6) 1437-1443
102 Spicer AP, Rowse GJ, Lidner TK, Gendler SJ. Delayed mammary tumor progression in Muc-1 null mice. J Biol Chem 1995; 270 (50) 30093-30101
103 Rochlitz C, Figlin R, Squiban P , et al. Phase I immunotherapy with a modified vaccinia virus (MVA) expressing human MUC1 as antigen-specific immunotherapy in patients with MUC1-positive advanced cancer. J Gene Med 2003; 5 (8) 690-699
104 Butts C, Murray RN, Smith CJ , et al. A multicenter open-label study to assess the safety of a new formulation of BLP25 liposome vaccine in patients with unresectable stage III non-small-cell lung cancer. Clin Lung Cancer 2010; 11 (6) 391-395
105 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): phase IIB randomized, multicenter, open-label trial. J Cancer Res Clin Oncol 2011; 137 (9) 1337-1342
106 Butts C. START: A phase III study of L-BLP25 cancer immunotherapy for unresectable stage III non-small cell lung cancer. J Clin Oncol 2013; 31 (15S):abstract 7500
107 Limacher J-M, Spring-Giusti C, Bellon N, Ancian P, Rooke R, Bonnefoy JY. Therapeutic cancer vaccines in the treatment of non-small-cell lung cancer. Expert Rev Vaccines 2013; 12 (3) 263-270
108 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. Lancet Oncol 2011; 12 (12) 1125-1133
109 Ramlau R, Quoix E, Rolski J , et al. A phase II study of Tg4010 (Mva-Muc1-Il2) in association with chemotherapy in patients with stage III/IV Non-small cell lung cancer. J Thorac Oncol 2008; 3 (7) 735-744
110 Nemunaitis J. Cancer targeting vaccines: surrogate measures of activity. Hum Vaccin Immunother 2013; 9 (1) 213-218
111 Quoix EA, Nemunaitis JJ, Burzykowski T, Bastien B, Lacoste G. TIME: A phase IIb/III randomized, double-blind, placebo-controlled study comparing first-line therapy with or without TG4010 immunotherapy product in patients with stage IV non-small cell lung cancer (NSCLC). J Clin Oncol 2012; 30 (15S):abstract TPS7610
112 Gure AO, Chua R, Williamson B , et al. Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer. Clin Cancer Res 2005; 11 (22) 8055-8062
113 Sienel W, Varwerk C, Linder A , et al. Melanoma associated antigen (MAGE)-A3 expression in stages I and II non-small cell lung cancer: results of a multi-center study. Eur J Cardiothorac Surg 2004; 25 (1) 131-134
114 Vantomme V, Dantinne C, Amrani N , et al. Immunologic analysis of a phase I/II study of vaccination with MAGE-3 protein combined with the AS02B adjuvant in patients with MAGE-3-positive tumors. J Immunother 2004; 27 (2) 124-135
115 Schultz ES, Lethé B, Cambiaso CL , et al. A MAGE-A3 peptide presented by HLA-DP4 is recognized on tumor cells by CD4+ cytolytic T lymphocytes. Cancer Res 2000; 60 (22) 6272-6275
116 Gaugler B, Van den Eynde B, van der Bruggen P , et al. Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes. J Exp Med 1994; 179 (3) 921-930
117 Vansteenkiste J, Zielinski M, Linder A , et al. Final results of a multi-center, double-blind, randomized, placebo-controlled phase II study to assess the efficacy of MAGE-A3 immunotherapeutic as adjuvant therapy in stage IB/II non-small cell lung cancer (NSCLC). J Clin Oncol 2007; 25 (18S):abstract 7554
118 Vansteenkiste J, Zielinski M, Dahabreh I , et al. Association of gene expression signature and clinical efficacy of MAGE-A3 antigenspecific cancer immunotherapeutic (ASCI) as adjuvant therapy in resected stage IB/II non-small cell lung cancer (NSCLC). J Clin Oncol 2008; 26 (15S):abstract 7501
119 Atanackovic D, Altorki NK, Cao Y , et al. Booster vaccination of cancer patients with MAGE-A3 protein reveals long-term immunological memory or tolerance depending on priming. Proc Natl Acad Sci U S A 2008; 105 (5) 1650-1655
120 Atanackovic D, Altorki N, Cao Y , et al. Booster vaccination of non-small cell lung cancer (NSCLC) patients with MAGEA3 protein and AS02B adjuvant. In ASCO Annual Meeting Proceedings Part I. J Clin Oncol 2007; 25 (18S):abstract 3015
121 De Pas T, Kim J-H, Zarogoulidis K , et al. MAGRIT phase III trial in adjuvant NSCLC: MAGE-A3 gene expression frequency on the first 2150 patients screened and demographics of first patients randomized. J Thorac Oncol 2009; 4 (9) S331-S332
122 Tyagi P, Mirakhur B. MAGRIT: the largest-ever phase III lung cancer trial aims to establish a novel tumor-specific approach to therapy. Clin Lung Cancer 2009; 10 (5) 371-374
123 Hobohm K, Seppmann T, Britten CM, Hoff H. Ninth annual meeting of the Association for Cancer Immunotherapy (CIMT 2011), May 25-27, 2011, Mainz, Germany. Cancer Immunol Immunother 2012; 61 (1) 137-143
124 van Cruijsen H, Ruiz MG, van der Valk P, de Gruijl TD, Giaccone G. Tissue micro array analysis of ganglioside N-glycolyl GM3 expression and signal transducer and activator of transcription (STAT)-3 activation in relation to dendritic cell infiltration and microvessel density in non-small cell lung cancer. BMC Cancer 2009; 9 (1) 180
125 Blanco R, Rengifo CE, Cedeño M, Frómeta M, Rengifo E, Carr A. Immunoreactivity of the 14F7 Mab (Raised against N-Glycolyl GM3 Ganglioside) as a positive prognostic factor in non-small-cell lung cancer. Patholog Res Int 2012; ;2012:235418. doi:10.1155/2012/235418. Epub 2012 Feb 26
126 de Leòn J, Fernández A, Mesa C, Clavel M, Fernández LE. Role of tumour-associated N-glycolylated variant of GM3 ganglioside in cancer progression: effect over CD4 expression on T cells. Cancer Immunol Immunother 2006; 55 (4) 443-450
127 Gomez DE, Vázquez AM, Alonso DF, Macías A. Anti-idiotype antibodies in cancer treatment. Front Oncol 2013; 3: 37 . doi:10.3389/fonc.2013.00037
128 Shaw AT, Yeap BY, Solomon BJ , et al. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol 2011; 12 (11) 1004-1012
129 Paez JG, Jänne PA, Lee JC , et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004; 304 (5676) 1497-1500
130 Sloan JA, Cella D, Frost M, Guyatt GH, Sprangers M, Symonds T ; Clinical Significance Consensus Meeting Group. Assessing clinical significance in measuring oncology patient quality of life: introduction to the symposium, content overview, and definition of terms. Mayo Clin Proc 2002; 77 (4) 367-370
131 Mina LA, Sledge Jr GW. Rethinking the metastatic cascade as a therapeutic target. Nat Rev Clin Oncol 2011; 8 (6) 325-332
132 Sledge Jr GW. The challenge and promise of the genomic era. J Clin Oncol 2012; 30 (2) 203-209
133 Ocaña A, Amir E, Vera F, Eisenhauer EA, Tannock IF. Addition of bevacizumab to chemotherapy for treatment of solid tumors: similar results but different conclusions. J Clin Oncol 2011; 29 (3) 254-256
134 Niraula S, Seruga B, Ocana A , et al. The price we pay for progress: a meta-analysis of harms of newly approved anticancer drugs. J Clin Oncol 2012; 30 (24) 3012-3019
135 Sullivan R, Peppercorn J, Sikora K , et al. Delivering affordable cancer care in high-income countries. Lancet Oncol 2011; 12 (10) 933-980
136 Ribas A, Hersey P, Middleton MR , et al. New challenges in endpoints for drug development in advanced melanoma. Clin Cancer Res 2012; 18 (2) 336-341
137 Stewart R, Mulgrew K, Wang S , et al. Blockade of PD-L1 Mediated Immunosupression for Cancer Therapy-MEDI4736, Monoclonal Antibody Discovery and Preclinical Development [abstract from 27th Annual Scientific Meeting of the Society for Immunotherapy of Cancer]. J Immunother 2012; 35 (9S) 765-766