An HPV-E6/E7 immunotherapy plus PD-1 checkpoint inhibition results in tumor regression and reduction in PD-L1 expression

Cancer Gene Therapy

Volumn 22, Issue 9, 2015, Pages 454-462

  Rice, A E ^a   Latchman, Y E ^a   Balint, J P ^a   Lee, J H ^b   Gabitzsch, E S ^a   Jones, F R ^a  

^a Etubics Corporation   (United States)

^b Sanford Cancer Center   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROGRAMMED DEATH 1 LIGAND 1; WART VIRUS VACCINE; CANCER VACCINE; CD274 PROTEIN, HUMAN; E6 PROTEIN, HUMAN PAPILLOMAVIRUS TYPE 16; IMMUNOGLOBULIN G; ONCOGENE PROTEIN E7, HUMAN PAPILLOMAVIRUS TYPE 16; ONCOPROTEIN; PROTEIN E7; REPRESSOR PROTEIN;

ADENOVIRIDAE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CONTROLLED STUDY; FEMALE; HUMAN PAPILLOMAVIRUS TYPE 16; IMMUNOTHERAPY; MOUSE; NONHUMAN; OVERALL SURVIVAL; PRIORITY JOURNAL; PROTEIN EXPRESSION; THERAPY EFFECT; TUMOR CELL; TUMOR MICROENVIRONMENT; TUMOR REGRESSION; VIRAL GENE DELIVERY SYSTEM; WART VIRUS; ANIMAL; ANTAGONISTS AND INHIBITORS; APOPTOSIS; BIOSYNTHESIS; C57BL MOUSE; CYTOTOXIC T LYMPHOCYTE; DRUG SCREENING; GENE EXPRESSION REGULATION; GENETICS; HUMAN; IMMUNOLOGY; LYMPHOCYTE COUNT; MULTIMODALITY CANCER THERAPY; PAPILLOMAVIRIDAE; PATHOLOGY; RAT; SATELLITE VIRUS; TUMOR ASSOCIATED LEUKOCYTE; TUMOR CELL LINE; TUMOR VIRUS INFECTIONS; UTERINE CERVICAL NEOPLASMS; VIROLOGY;

ANIMALS; ANTIGENS, CD274; APOPTOSIS; CANCER VACCINES; CELL LINE, TUMOR; COMBINED MODALITY THERAPY; DEFECTIVE VIRUSES; FEMALE; GENE EXPRESSION REGULATION; HUMANS; IMMUNOGLOBULIN G; IMMUNOTHERAPY; LYMPHOCYTE COUNT; LYMPHOCYTES, TUMOR-INFILTRATING; MICE; MICE, INBRED C57BL; ONCOGENE PROTEINS, VIRAL; PAPILLOMAVIRIDAE; PAPILLOMAVIRUS E7 PROTEINS; RATS; REPRESSOR PROTEINS; T-LYMPHOCYTES, CYTOTOXIC; TUMOR MICROENVIRONMENT; TUMOR VIRUS INFECTIONS; UTERINE CERVICAL NEOPLASMS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84942980828     PISSN: 09291903     EISSN: 14765500     Source Type: Journal    
DOI: 10.1038/cgt.2015.40     Document Type: Article

References (46)

1. Syrj?nen S. Human papillomavirus (HPV) in head and neck cancer. J Clin Virol 2005; 32: S59-S66.
2. Lu Y, Zhang Z, Liu Q, Liu B, Song X, Wang M et al. Immunological protection against HPV16 E7-expressing human esophageal cancer cell challenge by a novel HPV16-E6/E7 fusion protein based-vaccine in a Hu-PBL-SCID mouse model. Biol Pharm Bull 2007; 30: 150-156.
3. Lee DW, Anderson ME, Wu S, Lee JH. Development of an adenoviral vaccine against E6 and E7 oncoproteins to prevent growth of human papillomaviruspositive cancer. Arch Otolaryngol Head Neck Surg 2008; 134: 1316-1323.
4. Buscema J, Naghashfar Z, Sawada E, Daniel R, Woodruff JD, Shah K. The predominance of human papillomavirus type 16 in vulvar neoplasia. Obstet Gynecol 1988; 71: 601-606.
5. H?rding U, Junge J, Poulsen H, Lundvall F. Vulvar intraepithelial neoplasia III: a viral disease of undetermined progressive potential. Gynecol Oncol 1995; 56: 276-279.
6. Van Beurden M, Ten Kate FJW, Smits HL, Berkhout RJM, De Craen AJM, Van der Vange N et al. Multifocal vulvar intraepithelial neoplasia grade III and multicentric lower genital tract neoplasia is associated with transcriptionally active human papillomavirus. Cancer 1995; 75: 2879-2884.
7. Daling JR, Madeleine MM, Schwartz SM, Shera KA, Carter JJ, McKnight B et al. A population-based study of squamous cell vaginal cancer: HPV and cofactors. Gynecol Oncol 2002; 84: 263-270.
8. Devaraj K, Gillison ML, Wu T-C. Development of HPV vaccines for HPV-associated head and neck squamous cell carcinoma. Crit Rev Oral Biol Med 2003; 14: 345-362.
9. Marur S, D'Souza G, Westra WH, Forastiere AA. HPV-associated head and neck cancer: a virus-related cancer epidemic. Lancet Oncol 2010; 11: 781-789.
10. Psyrri A, DiMaio D. Human papillomavirus in cervical and head-and-neck cancer. Nat Clin Pract Oncol 2008; 5: 24-31.
11. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-T?n PF et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010; 363: 24-35.
12. Lehtinen M, Dillner J. Clinical trials of human papillomavirus vaccines and beyond. Nat Rev Clin Oncol 2013; 10: 400-410.
13. Monie A, Tsen S-WD, Hung C-F, Wu T-C, Therapeutic HPV. DNA vaccines. Expert Rev Vaccines 2009; 8: 1221-1235.
14. Bosch FX, Broker TR, Forman D, Moscicki A-B, Gillison ML, Doorbar J et al. Comprehensive control of human papillomavirus infections and related diseases. Vaccine 2013; 31: H1-H31.
15. Kawana K, Adachi K, Kojima S, Kozuma S, Fujii T. Therapeutic human papillomavirus (HPV) vaccines: a novel approach. Open Virol J 2012; 6: 264-269.
16. Wieking BG, Vermeer DW, Spanos WC, Lee KM, Vermeer P, Lee WT et al. A nononcogenic HPV 16 E6/E7 vaccine enhances treatment of HPV expressing tumors. Cancer Gene Ther 2012; 19: 667-674.
17. Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol 2005; 23: 515-548.
18. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12: 252-264.
19. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 2000; 192: 1027-1034.
20. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB et al. Tumorassociated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002; 8: 793-800.
21. Flies DB, Sandler BJ, Sznol M, Chen L. Blockade of the B7-H1/PD-1 pathway for cancer immunotherapy. Yale J Biol Med 2011; 84: 409-421.
22. Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 2008; 8: 467-477.
23. Song M, Chen D, Lu B, Wang C, Zhang J, Huang L et al. PTEN loss increases PD-L1 protein expression and affects the correlation between PD-L1 expression and clinical parameters in colorectal cancer. PLoS One 2013; 8: e65821.
24. Lyford-Pike S, Peng S, Young GD, Taube JM, Westra WH, Akpeng B et al. Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma. Cancer Res 2013; 73: 1733-1741.
25. Ukpo OC, Thorstad WL, Lewis JS. B7-H1 expression model for immune evasion in human papillomavirus-related oropharyngeal squamous cell carcinoma. Head Neck Pathol 2013; 7: 113-121.
26. Fu J, Malm IJ, Kadayakkara DK, Levitsky H, Pardoll D, Kim YJ. Preclinical evidence that PD1 blockade cooperates with cancer vaccine TEGVAX to elicit regression of established tumors. Cancer Res 2014; 74: 4042-4052.
27. Curran MA, Montalvo W, Yagita H, Allison JP. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci USA 2010; 107: 4275-4280.
28. Li B, Simmons A, Du T, Lin C, Moskalenko M, Gonzalez-Edick M et al. Allogeneic GM-CSF-secreting tumor cell immunotherapies generate potent anti-tumor responses comparable to autologous tumor cell immunotherapies. Clin Immunol 2009; 133: 184-197.
29. Amalfitano A, Hauser MA, Hu H, Serra D, Begy CR, Chamberlain JS. Production and characterization of improved adenovirus vectors with the E1, E2b, and E3 genes deleted. J Virol 1998; 72: 926-933.
30. Tomayko MM, Reynolds CP. Determination of subcutaneous tumor size in athymic (nude) mice. Cancer Chemother Pharmacol 1989; 24: 148-154.
31. Matsuzaki J, Gnjatic S, Mhawech-Fauceglia P, Beck A, Miller A, Tsuji T et al. Tumorinfiltrating NY-ESO-1-specific CD8+ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proc Natl Acad Sci USA 2010; 107: 7875-7880.
32. Woo SR, Turnis ME, Goldberg MV, Bankoti J, Selby M, Nirschl CJ et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res 2012; 72: 917-927.
33. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363: 711-723.
34. Hamid O, Robert C, Daud A, Hodi FS, Hwu W-J, Kefford R et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013; 369: 134-144.
35. Wolchok JD, Kluger H, Callahan MK, Postow Ma, Rizvi Na, Lesokhin AM et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013; 369: 122-133.
36. Rizvi NA, Mazi?res J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol 2015; 16: 257-265.
37. Hodi FS, Butler M, Oble DA, Seiden MV, Haluska FG, Kruse A et al. Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci USA 2008; 105: 3005-3010.
38. Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL et al. Colocalization of inflammatory response with B7-H1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 2012; 4: 127ra37-127ra37.
39. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF et al. Safety, activity, and immune correlates of Anti-PD-1 antibody in cancer. N Engl J Med 2012; 366: 2443-2454.
40. Baixeras E, Huard B, Miossec C, Jitsukawa S, Martin M, Hercend T et al. Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens. J Exp Med 1992; 176: 327-337.
41. Workman CJ, Rice DS, Dugger KJ, Kurschner C, Vignali DAA. Phenotypic analysis of the murine CD4-related glycoprotein, CD223 (LAG-3). Eur J Immunol 2002; 32: 2255-2263.
42. Huang CT, Workman CJ, Flies D, Pan X, Marson AL, Zhou G et al. Role of LAG-3 in regulatory T cells. Immunity 2004; 21: 503-513.
43. Workman CJ, Cauley LS, Kim I-J, Blackman MA, Woodland DL, Vignali DAA et al. Lymphocyte activation gene-3 (CD223) regulates the size of the expanding T cell population following antigen activation in vivo. J Immunol 2004; 172: 5450-5455.
44. Hannier S, Tournier M, Bismuth G, Triebel F. CD3/TCR complex-associated lymphocyte activation gene-3 molecules inhibit CD3/TCR signaling. J Immunol 1998; 161: 4058-4065.
45. Demeure CE, Wolfers J, Martin-Garcia N, Gaulard P, Triebel FT. Lymphocytes infiltrating various tumour types express the MHC class II ligand lymphocyte activation gene-3 (LAG-3): role of LAG-3/MHC class II interactions in cell-cell contacts. Eur J Cancer 2001; 37: 1709-1718.
46. Blackburn SD, Shin H, Haining WN, Zou T, Workman CJ, Polley A et al. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol 2009; 10: 29-37.