Non-clinical safety evaluation of repeated intramuscular administration of the AS15 immunostimulant combined with various antigens in rabbits and cynomolgus monkeys

Journal of Applied Toxicology

Volumn 36, Issue 2, 2016, Pages 238-256

  Garcon N ^a,b   Silvano, J ^c   Kuper, C F ^d   Baudson, N ^a   Gerard C ^a   Forster, R ^c   Segal, L ^a  

^a GSK   (Belgium)

^b BIOASTER   (France)

^c SOLVO BIOTECHNOLOGY   (Hungary)

^d TNO   (Netherlands)

Author keywords

Antigen specific cancer immunotherapy; AS15; HER2; Immunostimulant; P501; PRAME; WT1

Indexed keywords

ALBUMIN; AS 15; BILIRUBIN; CREATININE; EPIDERMAL GROWTH FACTOR RECEPTOR 2; FIBRINOGEN; GLOBULIN; IMMUNOSTIMULATING AGENT; PROTEIN P501; PROTEIN PRAME; TESTOSTERONE; TUMOR ANTIGEN; UNCLASSIFIED DRUG; UREA; IMMUNOLOGICAL ADJUVANT;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AXILLARY LYMPH NODE; BODY TEMPERATURE; CONTROLLED STUDY; EDEMA; ELECTROCARDIOGRAPHY; ENZYME LINKED IMMUNOSORBENT ASSAY; ERYTHEMA; EVALUATION STUDY; FEMALE; HEART VENTRICLE EXTRASYSTOLE; IMMUNOHISTOCHEMISTRY; MACACA FASCICULARIS; MALE; NEUTROPHIL COUNT; NONHUMAN; ORGAN WEIGHT; PRIORITY JOURNAL; PROSTATE; PROTEIN EXPRESSION; RABBIT; SEROCONVERSION; TOXICITY TESTING; WEIGHT GAIN; YOUNG ADULT; ANIMAL; CLINICAL TRIAL; HAPLORHINI; IMMUNOLOGY; INTRAMUSCULAR DRUG ADMINISTRATION; NEOPLASMS;

ADJUVANTS, IMMUNOLOGIC; ANIMALS; ANTIGENS, NEOPLASM; FEMALE; HAPLORHINI; INJECTIONS, INTRAMUSCULAR; MALE; MODELS, ANIMAL; NEOPLASMS; RABBITS;

EID: 84954387067     PISSN: 0260437X     EISSN: 10991263     Source Type: Journal    
DOI: 10.1002/jat.3167     Document Type: Article

References (53)

1. Aldrich JF, Lowe DB, Shearer MH, Winn RE, Jumper CA, Kennedy RC. 2010. Vaccines and immunotherapeutics for the treatment of malignant disease. Clin. Dev. Immunol. 2010: 697158.
2. Bilusic M, Gulley JL. 2012. Endpoints, patient selection, and biomarkers in the design of clinical trials for cancer vaccines. Cancer Immunol. Immunother. 61: 109-117.
3. Brody JD, Ai WZ, Czerwinski DK, Torchia JA, Levy M, Advani RH, Kim YH, Hoppe RT, Knox SJ, Shin LK, Wapnir I, Tibshirani RJ, Levy R. 2010. In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a phase I/II study. J. Clin. Oncol. 28: 4324-4332.
4. Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH, et al. 1990. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell 60: 509-520.
5. Chapin RE, Creasy DM. 2012. Assessment of circulating hormones in regulatory toxicity studies II. Male reproductive hormones. Toxicol. Pathol. 40: 1063-1078.
6. Cluff CW. 2010. Monophosphoryl lipid A (MPL) as an adjuvant for anti-cancer vaccines: clinical results. Adv. Exp. Med. Biol. 667: 111-123.
7. Cooper CL, Davis HL, Morris ML, Efler SM, Adhami MA, Krieg AM, Cameron DW, Heathcote J. 2004a. CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B HBV vaccine in healthy adults: a double-blind phase I/II study. J. Clin. Immunol. 24: 693-701.
8. Cooper CL, Davis HL, Morris ML, Efler SM, Krieg AM, Li Y, Laframboise C, Al Adhami MJ, Khaliq Y, Seguin I, Cameron DW. 2004b. Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine. Vaccine 22: 3136-3143.
9. Destexhe E, Grosdidier E, Baudson N, Forster R, Gerard C, Garcon N, Segal L. 2014a. Non-clinical safety evaluation of single and repeated intramuscular administrations of MAGE-A3 Cancer Immunotherapeutic in rabbits and cynomolgus monkeys. J. Appl. Toxicol. Sep 12. DOI: 10.1002/jat.3025
10. Destexhe E, Stannard D, Wilby OK, Grosdidier E, Baudson N, Forster R, Gérard CM, Garçon N, Segal L. 2014b. Nonclinical reproductive and developmental safety evaluation of the MAGE-A3 Cancer Immunotherapeutic, a therapeutic vaccine for cancer treatment. Reprod. Toxicol. 51C: 90-105.
11. Didierlaurent AM, Morel S, Lockman L, Giannini SL, Bisteau M, Carlsen H, Kielland A, Vosters O, Vanderheyde N, Schiavetti F, Larocque D, Van Mechelen M, Garçon N. 2009. AS04, an aluminum salt- and TLR4 agonist-based adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity. J. Immunol. 183: 6186-6197.
12. Didierlaurent AM, Collignon C, Bourguignon P, Wouters S, Fierens K, Fochesato M, Dendouga N, Langlet C, Malissen B, Lambrecht BN, Garçon N, Van Mechelen M, Morel S. 2014. Enhancement of adaptive immunity by the human vaccine adjuvant AS01 depends on activated dendritic cells. J. Immunol. 193: 1920-1930.
13. Dimberu PM, Leonhardt RM. 2011. Cancer immunotherapy takes a multi-faceted approach to kick the immune system into gear. Yale J. Biol. Med. 84: 371-380.
14. European Agency for the Evaluation of Medicinal Products (EMA). Committee for Proprietary Medicinal Products (CPMP). 1997. Note for guidance on preclinical pharmacological and toxicological testing of vaccines. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/10/WC500004004.pdf (accessed 27 February 2014).
15. European Agency for the Evaluation of Medicinal Products (EMA). Committee for Proprietary Medicinal Products (CPMP). 1999. ICH Topic S 4 Duration of Chronic Toxicity Testing in Animals (Rodent and Non Rodent Toxicity Testing). Note for Guidance on Duration of Chronic Toxicity Testing in Animals (Rodent and Non Rodent Toxicity Testing (CPMP/ICH/300/95). http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002800.pdf (accessed 27 February 2014).
16. European Agency for the Evaluation of Medicinal Products (EMA). Committee for proprietary Medicinal Products (CPMP). 2000. Note for guidance on repeated dose toxicity. CPMP/SWP/1042/99. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003102.pdf (accessed 27 February 2014).
17. European Agency for the Evaluation of Medicinal Products (EMA). 2001. Note for guidance on non-clinical local tolerance testing of medicinal products (CPMP/SWP/2145/00). http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003315.pdf (accessed 27 February 2014).
18. European Agency for the Evaluation of Medicinal Products (EMA). Committee for proprietary Medicinal Products (CPMP). 2005. Guideline on adjuvants in vaccines for human use. 2005. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003809.pdf (accessed 13 February 2015).
19. Epping MT, Bernards R. 2006. A causal role for the human tumor antigen preferentially expressed antigen of melanoma in cancer. Cancer Res. 66: 10639-10642.
20. Epping MT, Wang L, Edel MJ, Carlee L, Hernandez M, Bernards R. 2005. The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell 122: 835-847.
21. Forster R. 2012. Study designs for the nonclinical safety testing of new vaccine products. J. Pharmacol. Toxicol. Methods 66: 1-7.
22. Gessler M, Poustka A, Cavenee W, Neve RL, Orkin SH, Bruns GA. 1990. Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. Nature 343: 774-778.
23. Gutzmer R, Rivoltini L, Levchenko E, Testori A, Utikal J, Ascierto P, Salaun B, Vanhoutte N, Gillet M, Brichard V. 2012. Immunogenicity and safety of the PRAME Immunotherapeutic in metastatic melanoma: A phase I/II dose escalation study. Ann. Oncol. 23(Suppl. 9): 1110.
24. Hamilton E, Blackwell K, Hobeika AC, Clay TM, Broadwater G, Ren XR, Chen W, Castro H, Lehmann F, Spector N, Wei J, Osada T, Lyerly HK, Morse MA. 2012. Phase 1 clinical trial of HER2-specific immunotherapy with concomitant HER2 kinase inhibition [corrected]. J. Transl. Med. 10: 28.
25. Haruyama E, Suda M, Ayukawa Y, Kamura K, Mizutamari M, Ooshima Y, Tanimoto A. 2012. Testicular development in cynomolgus monkeys. Toxicol. Pathol. 40: 935-942.
26. Klinman DM, Xie H, Ivins BE. 2006. CpG oligonucleotides improve the protective immune response induced by the licensed anthrax vaccine. Ann. N. Y. Acad. Sci. 1082: 137-150.
27. Krieg AM, Efler SM, Wittpoth M, Al Adhami MJ, Davis HL. 2004. Induction of systemic TH1-like innate immunity in normal volunteers following subcutaneous but not intravenous administration of CPG 7909, a synthetic B-class CpG oligodeoxynucleotide TLR9 agonist. J. Immunother. 27: 460-471.
28. Kruit WH, Suciu S, Dreno B, Mortier L, Robert C, Chiarion-Sileni V, Maio M, Testori A, Dorval T, Grob JJ, Becker JC, Spatz A, Eggermont AM, Louahed J, Lehmann FF, Brichard VG, Keilholz U. 2013. Selection of immunostimulant AS15 for active immunization with MAGE-A3 protein: results of a randomized phase II study of the European Organisation for Research and Treatment of Cancer Melanoma Group in Metastatic Melanoma. J. Clin. Oncol. 31: 2413-2420.
29. Ku WW, Pagliusi F, Foley G, Roesler A, Zimmerman T. 2010. A simple orchidometric method for the preliminary assessment of maturity status in male cynomolgus monkeys (Macaca fascicularis) used for nonclinical safety studies. J. Pharmacol. Toxicol. Methods 61: 32-37.
30. Lane Z, Hansel DE, Epstein JI. 2008. Immunohistochemical expression of prostatic antigens in adenocarcinoma and villous adenoma of the urinary bladder. Am. J. Surg. Pathol. 32: 1322-1326.
31. Lee SB, Haber DA. 2001. Wilms tumor and the WT1 gene. Exp. Cell Res. 264: 74-99.
32. Ministère de l'Emploi et de la Solidarité. 2000. ARRÊTÉ DU 14 MARS 2000 relatif aux bonnes pratiques de laboratoire. http://ansm.sante.fr/var/ansm_site/storage/original/application/dd4641e3edd1885e60f0337d4c385b5e.pdf (accessed 27 February 2014).
33. Morel S, Didierlaurent A, Bourguignon P, Delhaye S, Baras B, Jacob V, Planty C, Elouahabi A, Harvengt P, Carlsen H, Kielland A, Chomez P, Garçon N, Van Mechelen M. 2011. Adjuvant System AS03 containing alpha-tocopherol modulates innate immune response and leads to improved adaptive immunity. Vaccine 29: 2461-2473.
34. Mullen GE, Ellis RD, Miura K, Malkin E, Nolan C, Hay M, Fay MP, Saul A, Zhu D, Rausch K, Moretz S, Zhou H, Long CA, Miller LH, Treanor J. 2008. Phase 1 trial of AMA1-C1/Alhydrogel plus CPG 7909: an asexual blood-stage vaccine for Plasmodium falciparum malaria. PLoS One 3: e2940.
35. Nasomyon T, Samphao S, Sangkhathat S, Mahattanobon S, Graidist P. 2014. Correlation of Wilms' tumor 1 isoforms with HER2 and ER-alpha and its oncogenic role in breast cancer. Anticancer Res 34: 1333-1342.
36. OECD. 1998. Organisation for Economic Co-operation and Development. OECD SERIES ON PRINCIPLES OF GOOD LABORATORY PRACTICE AND COMPLIANCE MONITORING. OECD Principles on Good Laboratory Practice (as revised in 1997) (ENV/MC/CHEM(98)17).
37. Oka Y, Tsuboi A, Elisseeva OA, Udaka K, Sugiyama H. 2002. WT1 as a novel target antigen for cancer immunotherapy. Curr. Cancer Drug Targets 2: 45-54.
38. Pilon-Thomas S, Li W, Briggs JJ, Djeu J, Mule JJ, Riker AI. 2006. Immunostimulatory effects of CpG-ODN upon dendritic cell-based immunotherapy in a murine melanoma model. J. Immunother. 29: 381-387.
39. Pujol J-L, De Pas T, Rittmeyer A, Kubisa B, Vallieres E, Levchenko E, Salaun B, Vanhoutte N, Debois M, Brichard V. 2012. Immunogenicity and safety of the PRAME Cancer Immunotherapeutic in non-small cell lung cancer (NSCLC): A phase I dose escalation study. Ann. Oncol. 23(Suppl. 9): ix386 (abs1182P).
40. Segal L, Morelle D, Blee M, Moore E, Damsten M, Liu KC, Destexhe E, Garçon N. 2015. Local tolerance and systemic toxicity of single and repeated intramuscular administrations of two different formulations of the RTS, S malaria candidate vaccine in rabbits. Regul. Toxicol. Pharmacol. 71: 269-278.
41. Sheridan T, Herawi M, Epstein JI, Illei PB. 2007. The role of P501S and PSA in the diagnosis of metastatic adenocarcinoma of the prostate. Am. J. Surg. Pathol. 31: 1351-1355.
42. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. 1987. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235: 177-182.
43. Speiser DE, Lienard D, Rufer N, Rubio-Godoy V, Rimoldi D, Lejeune F, Krieg AM, Cerottini JC, Romero P. 2005. Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909. J. Clin. Invest. 115: 739-746.
44. Stewart VA, McGrath S, Krieg AM, Larson NS, Angov E, Smith CL, Brewer TG, Heppner DG Jr. 2008. Activation of innate immunity in healthy Macaca mulatta macaques by a single subcutaneous dose of GMP CpG 7909: safety data and interferon-inducible protein-10 kinetics for humans and macaques. Clin. Vaccine Immunol. 15: 221-226.
45. Thuilliez C, Dorso L, Howroyd P, Gould S, Chanut F, Burnett R. 2009. Histopathological lesions following intramuscular administration of saline in laboratory rodents and rabbits. Exp. Toxicol. Pathol. 61: 13-21.
46. The European Parliament and the Council of the European Union. 2004. DIRECTIVE 2004/10/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 11 February 2004. Official Journal of the European Union. L 50/59. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2004:050:0028:0028:EN:PDF (accessed 27 February 2014).
47. The Commission of the European Communities. 1999. Commission Directive 1999/11/EC of 8 March 1999. Official Journal of the European Communities L 77. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:1999:077:0008:0021:EN:PDF (accepted 27 February 2014).
48. The Council of the European Communities. 1986. Council Directive of 24 November 1986. http://ec.europa.eu/food/fs/aw/aw_legislation/scientific/86-609-eec_en.pdf (accessed 27 February 2014).
49. Valmori D, Souleimanian NE, Tosello V, Bhardwaj N, Adams S, O'Neill D, Pavlick A, Escalon JB, Cruz CM, Angiulli A, Angiulli F, Mears G, Vogel SM, Pan L, Jungbluth AA, Hoffmann EW, Venhaus R, Ritter G, Old LJ, Ayyoub M. 2007. Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming. Proc. Natl. Acad. Sci. U. S. A. 104: 8947-8952.
50. Weeratna RD, McCluskie MJ, Xu Y, Davis HL. 2000. CpG DNA induces stronger immune responses with less toxicity than other adjuvants. Vaccine 18: 1755-1762.
51. Weir GM, Liwski RS, Mansour M. 2011. Immune modulation by chemotherapy or immunotherapy to enhance cancer vaccines. Cancers (Basel) 3: 3114-3142.
52. World Health Organization (WHO). 2003. WHO guidelines on nonclinical evaluation of vaccines. http://www.who.int/biologicals/publications/nonclinical_evaluation_vaccines_nov_2003.pdf (accessed 27 February 2014).
53. Xu C, Wu C, Xia Y, Zhong Z, Liu X, Xu J, Cui F, Chen B, Roe OD, Li A, Chen Y. 2013. WT1 promotes cell proliferation in non-small cell lung cancer cell lines through up-regulating cyclin D1 and p-pRb in vitro and in vivo. PLoS One 8: e68837.