Intratumoral delivery of low doses of anti-CD40 mAb combined with monophosphoryl lipid a induces local and systemic antitumor effects in immunocompetent and T cell-deficient mice

Journal of Immunotherapy

Volumn 36, Issue 1, 2013, Pages 29-40

  Van De Voort, Tyler J ^a   Felder, Mildred A R ^a   Yang, Richard K ^a   Sondel, Paul M ^a   Rakhmilevich, Alexander L ^a  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

anti CD40; immunotherapy; intratumoral; macrophages; monophosphoryl lipid A

Indexed keywords

MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY CD40; PHOSPHORYL LIPID A; TOLL LIKE RECEPTOR 4; UNCLASSIFIED DRUG;

ADOLESCENT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; C57BL 6 MOUSE; CANCER CHEMOTHERAPY; CANCER INHIBITION; CONTROLLED STUDY; DRUG DOSE REDUCTION; DRUG DOSE TITRATION; DRUG MEGADOSE; FEMALE; IMMUNE DEFICIENCY; IMMUNOMODULATION; LOW DRUG DOSE; MACROPHAGE; MELANOMA; MOUSE; NONHUMAN; PRIORITY JOURNAL; SECOND CANCER; T LYMPHOCYTE;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIGENS, CD40; ANTINEOPLASTIC AGENTS; FEMALE; IMMUNOGLOBULIN G; IMMUNOSUPPRESSION; IMMUNOTHERAPY; LIPID A; MACROPHAGES; MELANOMA, EXPERIMENTAL; MICE; MICE, INBRED C57BL; MICE, SCID; PERITONEAL CAVITY; T-LYMPHOCYTES; TOLL-LIKE RECEPTOR 4;

EID: 84871922810     PISSN: 15249557     EISSN: 15374513     Source Type: Journal    
DOI: 10.1097/CJI.0b013e3182780f61     Document Type: Article

References (48)

1. Tong AW, Stone MJ. Prospects for CD40-directed experimentaltherapy of human cancer. Cancer Gene Ther. 2003;10:1-13 (Pubitemid 36222071)
2. Weiner LM, Surana R, Murray J. Vaccine prevention ofcancer: can endogenous antigens be targeted? Cancer Prev Res.2010;3:410-415
3. Solomayer E-F, Feuerer M, Bai L, et al. Influence of adjuvanthormone therapy and chemotherapy on the immune systemanalysed in the bone marrow of patients with breast cancer.Clin Cancer Res. 2003;9:174-180 (Pubitemid 36109730)
4. Speiser DE. Self antigens expressed by solid tumors do notefficiently stimulate naive or activated T cells: Implications forimmunotherapy. J Exp Med. 1997;186:645-653 (Pubitemid 27381529)
5. Baldridge JR, Crane RT. Monophosphoryl lipid A (MPL)formulations for the next generation of vaccines. Methods.1999;19:103-107 (Pubitemid 29497759)
6. Whiteside TL. Immune suppression in cancer: effects onimmune cells, mechanisms and future therapeutic intervention.Semin Cancer Biol. 2006;16:3-15 (Pubitemid 43139705)
7. Rosenberg S a, Yang JC, Restifo NP. Cancer immunotherapy:moving beyond current vaccines. Nat Med. 2004;10:909-915 (Pubitemid 39273730)
8. Stewart TJ, Smyth MJ. Improving cancer immunotherapy bytargeting tumor-induced immune suppression. Cancer MetastRev. 2011;30:125-140
9. Harris J, Sengar D, Stewart T, et al. The effect ofimmunosuppressive chemotherapy on immune function inpatients with malignant disease. Cancer. 1976;37(suppl):1058-1069
10. Nair RE, Kilinc MO, Jones SA, et al. Chronic immune therapyinduces a progressive increase in intratumoral T suppressoractivity and a concurrent loss of tumor-specific CD8+ Teffectors in her-2/neu transgenic mice bearing advancedspontaneous tumors. J Immunol. 2006;176:7325-7334 (Pubitemid 43849033)
11. Johnson EE, Buhtoiarov IN, Baldeshwiler MJ, et al. EnhancedT-cell- independent antitumor effect of cyclophosphamidecombined with anti-CD40 mAb and CpG in mice. J Immunother.2011;34:76-84
12. Buhtoiarov IN, Lum H, Berke G, et al. CD40 ligation activatesmurine macrophages via an IFN-gamma-dependent mechanismresulting in tumor cell destruction in vitro. J Immunol.2005;174:6013-6022 (Pubitemid 40663788)
13. Lum HD, Buhtoiarov IN, Schmidt BE, et al. In vivo CD40ligation can induce T-cell-independent antitumor effects thatinvolve macrophages. J Leukocyte Biol. 2006;79:1181-1192 (Pubitemid 44835552)
14. Buhtoiarov IN, Lum HD, Berke G, et al. Synergistic activationof macrophages via CD40 and TLR9 results in T cellindependent antitumor effects. J Immunol. 2006;176:309-318 (Pubitemid 43023276)
15. Beatty GL, Chiorean EG, Fishman MP, et al. CD40 agonistsalter tumor stroma and show efficacy against pancreaticcarcinoma in mice and humans. Science. 2011;331:1612-1616
16. Nierkens S, den Brok MH, Roelofsen T, et al. Route ofadministration of the TLR9 agonist CpG critically determinesthe efficacy of cancer immunotherapy in mice. PLoS One.2009;4:e8368
17. Cooper CL, Davis HL, Morris ML, et al. CPG 7909, animmunostimulatory TLR9 agonist oligodeoxynucleotide, asadjuvant to Engerix-B HBV vaccine in healthy adults: adouble-blind phase I/II study. J Clin Immunol. 2004;24:693-701 (Pubitemid 40933121)
18. Buhtoiarov IN, Sondel PM, Eickhoff JC, et al. Macrophagesare essential for antitumour effects against weakly immunogenicmurine tumours induced by class B CpG-oligodeoxynucleotides.Immunology. 2007;120:412-423 (Pubitemid 46232916)
19. Ulevitch RJ. Therapeutics targeting the innate immune system.Nat Rev Immunol. 2004;4:512-520 (Pubitemid 38931766)
20. Campbell JD, Cho Y, Foster ML, et al. CpG-containingimmunostimulatory DNA sequences elicit TNF-alpha-dependenttoxicity in rodents but not in humans. J Clin Invest.2009;119:2564-2576
21. Sweet MJ, Hume DA. Bacterial lipopolysaccharide confersresistance to G418, doxorubicin, and taxol in the murinemacrophage cell line, RAW264. J Leukocyte Biol. 1996;59:280-286 (Pubitemid 126484102)
22. Bode JG, Ehlting C, Ha? ussinger D. The macrophage responsetowards LPS and its control through the p38(MAPK)-STAT3 axis. Cell Signal. 2012;24:1185-1194
23. Ribi E, Milner KC, Granger DL, et al. Immunotherapy withnonviable microbial components. Ann NY Acad Sci. 1976;277:228-238
24. Masihi KN, Lange W, Brehmer W, et al. Immunobiologicalactivities of nontoxic lipid A: enhancement of nonspecificresistance in combination with trehalose dimycolate againstviral infection and adjuvant effects. Int Immunopharmacol.1986;8:339-345 (Pubitemid 16063773)
25. Baldridge JR, McGowan P, Evans JT, et al. Taking a Toll onhuman disease: toll-like receptor 4 agonists as vaccineadjuvants and monotherapeutic agents. Expert Opin Biol Ther.2004;4:1129-1138 (Pubitemid 38937554)
26. Vandepapelière P, Horsmans Y, Moris P, et al. Vaccineadjuvant systems containing monophosphoryl lipid A andQS21 induce strong and persistent humoral and T cellresponses against hepatitis B surface antigen in healthy adultvolunteers. Vaccine. 2008;26:1375-1386
27. Persing DH, Coler RN, Lacy MJ, et al. Taking toll: lipid Amimetics as adjuvants and immunomodulators. Trends Microbiol.2002;10:s32-s37
28. Garcon N, Leo O. Innate immunity and vaccine adjuvants:from concepts to the development of a unique adjuvant systemAS04 used for the formulation of a human papillomavirus(HPV) vaccine. Curr Cancer Ther Rev. 2010;6:126-137
29. Evans JT, Cluff CW, Johnson DA, et al. Enhancement ofantigen-specific immunity via the TLR4 ligands MPL adjuvantand Ribi. Expert Rev Vaccines. 2003;2:219-229 (Pubitemid 36559927)
30. Didierlaurent AM, Morel S, Lockman L, et al. AS04, analuminum salt-and TLR4 agonist-based adjuvant system,induces a transient localized innate immune response leading toenhanced adaptive immunity. J Immunol. 2009;183:6186-6197
31. Baker PJ, Hiernaux JR, Fauntleroy MB, et al. Inactivation ofsuppressor T-cell activity by nontoxic monophosphoryllipid A. Infect Immun. 1988;56:1076-1083
32. Rakhmilevich AL, Buhtoiarov IN, Malkovsky M, et al. CD40ligation in vivo can induce T cell independent antitumor effectseven against immunogenic tumors. Cancer Immunol Immunother.2008;57:1151-1160
33. Hyakushima N, Mitsuzawa H, Nishitani C, et al. Interactionof soluble form of recombinant extracellular TLR4 domainwith MD-2 enables lipopolysaccharide binding and attenuatesTLR4-mediated signaling. J Immunol. 2004;173:6949-6954 (Pubitemid 39541083)
34. Rakhmilevich AL, Baldeshwiler MJ, Van De Voort TJ, et al.Tumor-associated myeloid cells can be activated in vitro andin vivo to mediate antitumor effects. Cancer Immunol Immunother.2012;61:1683-1697
35. Lou Y, Liu C, Lize G, et al. Antitumor activity mediated byCpG: the route of administration is critical. J Immunother.2011;34:279-288
36. Johnson EE, Lum HD, Rakhmilevich AL, et al. Intratumoralimmunocytokine treatment results in enhanced antitumoreffects. Cancer Immunol Immunother. 2008;57:1891-1902
37. Vonderheide RH, Flaherty KT, Khalil M, et al. Clinicalactivity and immune modulation in cancer patients treatedwith CP-870,893, a novel CD40 agonist monoclonal antibody.J Clin Oncol. 2007;25:876-883 (Pubitemid 350002889)
38. Cluff CW. Monophosphoryl lipid A (MPL) as an adjuvant foranti-cancer vaccines: clinical results. Adv Exp Med Biol.2010;667:111-123
39. Turner JG, Rakhmilevich AL, Burdelya L, et al. Anti-CD40antibody induces antitumor and antimetastatic effects: the roleof NK cells. J Immunol. 2001;166:89-94 (Pubitemid 32038420)
40. Lum HD, Buhtoiarov IN, Schmidt BE, et al. Tumoristaticeffects of anti-CD40 mAb-activated macrophages involvenitric oxide and tumour necrosis factor-alpha. Immunology.2006;118:261-270 (Pubitemid 43727432)
41. Fonsatti E, Maio M, Altomonte M, et al. Biology and clinicalapplications of CD40 in cancer treatment. Semin Oncol.2010;37:517-523
42. Vosika GJ, Barr C, Gilbertson D. Phase-I study of intravenousmodified lipid A. Cancer Immunol Immunother. 1984;18:107-112
43. Qureshi N, Takayama K, Ribi E. Purification and structuraldetermination of nontoxic lipid A obtained from the lipopolysaccharideof Salmonella typhimurium. J Biol Chem.1982;257:11808-11815 (Pubitemid 13218648)
44. Johnson AG. Molecular adjuvants and immunomodulators:new approaches to immunization. Clin Microbiol Rev.1994;7:277-289 (Pubitemid 24216121)
45. Liu G, Ma H, Qiu L, et al. Phenotypic and functional switch ofmacrophages induced by regulatory CD4+CD25+ T cellsin mice. Immunol Cell Biol. 2011;89:130-142
46. Khalil M, Vonderheide RH. Anti-CD40 agonist antibodies:preclinical and clinical experience. Update Cancer Ther.2007;2:61-65 (Pubitemid 47393664)
47. Buhtoiarov IN, Sondel PM, Wigginton JM, et al. Anti-tumoursynergy of cytotoxic chemotherapy and anti-CD40 plus CpGODNimmunotherapy through repolarization of tumourassociatedmacrophages. Immunology. 2011;132:226-239
48. Stone GW, Barzee S, Snarsky V, et al. Nanoparticle-deliveredmultimeric soluble CD40L DNA combined with toll-likereceptor agonists as a treatment for melanoma. PLoS One.2009;4:e7334