Immunotherapy with MVA-BN ®-HER2 induces HER-2-specific Th1 immunity and alters the intratumoral balance of effector and regulatory T cells

Cancer Immunology, Immunotherapy

Volumn 61, Issue 1, 2012, Pages 19-29

  Mandl, Stefanie J ^a   Rountree, Ryan B ^a   Dalpozzo, Katie ^a   Do, Lisa ^a   Lombardo, John R ^a   Schoonmaker, Peter L ^a   Dirmeier, Ulrike ^b   Steigerwald, Robin ^b   Giffon, Thierry ^a   Laus, Reiner ^a   Delcayre, Alain ^a  

^a BN ImmunoTherapeutics ^*  (United States)

^b Bavarian Nordic GmbH   (Germany)

Author keywords

Breast cancer; HER 2; Immunosuppression; Immunotherapy; Modified Vaccinia Ankara (MVA); Regulatory T cells; Th1

Indexed keywords

CANCER VACCINE; EPIDERMAL GROWTH FACTOR RECEPTOR 2; GLYCOPROTEIN P 15095; MVA BN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIBODY RESPONSE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER IMMUNOTHERAPY; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; COLON CARCINOMA; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFICACY; EFFECTOR CELL; FEMALE; IMMUNOGENICITY; LUNG METASTASIS; LYMPHOCYTIC INFILTRATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; SINGLE DRUG DOSE; T CELL DEPLETION; T LYMPHOCYTE ACTIVATION; TH1 CELL;

ADENOCARCINOMA; ANIMALS; B-LYMPHOCYTE SUBSETS; CANCER VACCINES; CELL LINE, TUMOR; COLONIC NEOPLASMS; DISEASE MODELS, ANIMAL; FEMALE; HUMANS; IMMUNOPHENOTYPING; IMMUNOTHERAPY; LUNG NEOPLASMS; LYMPHOCYTE ACTIVATION; MICE; MICE, INBRED BALB C; RECEPTOR, ERBB-2; T-LYMPHOCYTES, REGULATORY;

EID: 84856725254     PISSN: 03407004     EISSN: 14320851     Source Type: Journal    
DOI: 10.1007/s00262-011-1077-4     Document Type: Article

References (48)

1. JS Kennedy RN Greenberg 2009 IMVAMUNE: modified vaccinia Ankara strain as an attenuated smallpox vaccine Expert Rev Vaccines 8 13 24 19093767 10.1586/14760584.8.1.13 1:CAS:528:DC%2BD1cXhsFWjt7nL
2. V Renard L Sonderbye K Ebbehoj PB Rasmussen K Gregorius, et al. 2003 HER-2 DNA and protein vaccines containing potent Th cell epitopes induce distinct protective and therapeutic antitumor responses in HER-2 transgenic mice J Immunol 171 1588 1595 12874253 1:CAS:528:DC%2BD3sXlsFylu7Y%3D (Pubitemid 36900095)
3. RR Brutkiewicz SJ Klaus RM Welsh 1992 Window of vulnerability of vaccinia virus-infected cells to natural killer (NK) cell-mediated cytolysis correlates with enhanced NK cell triggering and is concomitant with a decrease in H-2 class I antigen expression Nat Immun 11 203 214 1421956 1:STN:280: DyaK3s%2FksVSksg%3D%3D
4. AO Dokun DT Chu L Yang AS Bendelac WM Yokoyama 2001 Analysis of in situ NK cell responses during viral infection J Immunol 167 5286 5293 11673544 1:CAS:528:DC%2BD3MXotVWjsbk%3D (Pubitemid 33009767)
5. AO Dokun S Kim HR Smith HS Kang DT Chu, et al. 2001 Specific and nonspecific NK cell activation during virus infection Nat Immunol 2 951 956 11550009 10.1038/ni714 1:CAS:528:DC%2BD3MXnsVCis78%3D (Pubitemid 32976168)
6. PL Earl JL Americo LS Wyatt LA Eller JC Whitbeck, et al. 2004 Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox Nature 428 182 185 15014500 10.1038/nature02331 1:CAS:528:DC%2BD2cXhvFClsrk%3D (Pubitemid 38374314)
7. LS Wyatt PL Earl LA Eller B Moss 2004 Highly attenuated smallpox vaccine protects mice with and without immune deficiencies against pathogenic vaccinia virus challenge Proc Natl Acad Sci U S A 101 4590 4595 15070762 10.1073/pnas.0401165101 1:CAS:528:DC%2BD2cXjtFKis7Y%3D (Pubitemid 38437455)
8. LM Coussens Z Werb 2002 Inflammation and cancer Nature 420 860 867 12490959 10.1038/nature01322 1:CAS:528:DC%2BD38XpsFygtb4%3D (Pubitemid 36019639)
9. KE de Visser 2008 Spontaneous immune responses to sporadic tumors: tumor-promoting, tumor-protective or both? Cancer Immunol Immunother 57 1531 1539 18343921 10.1007/s00262-008-0501-x 1:CAS:528:DC%2BD1cXovFyisb0%3D
10. KE de Visser LM Coussens 2006 The inflammatory tumor microenvironment and its impact on cancer development Contrib Microbiol 13 118 137 16627962 10.1159/000092969
11. S Gross A Geldmacher T Sharav F Losch P Walden 2009 Immunosuppressive mechanisms in cancer: consequences for the development of therapeutic vaccines Vaccine 27 3398 3400 19200836 10.1016/j.vaccine.2009.01.070 1:CAS:528: DC%2BD1MXmtlKgu7k%3D
12. Egeblad M, Nakasone ES, Werb Z (2010) Tumors as organs: complex tissues that interface with the entire organism. Dev Cell 18:884-901
13. EY Woo H Yeh CS Chu K Schlienger RG Carroll, et al. 2002 Cutting edge: regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation J Immunol 168 4272 4276 11970966 1:CAS:528:DC%2BD38Xjt12jsLo%3D (Pubitemid 34441324)
14. BG Barnett J Ruter I Kryczek MJ Brumlik PJ Cheng, et al. 2008 Regulatory T cells: a new frontier in cancer immunotherapy Adv Exp Med Biol 622 255 260 18546633 10.1007/978-0-387-68969-2-20 1:CAS:528:DC%2BC3cXhtlKisb3K
15. TJ Curiel G Coukos L Zou X Alvarez P Cheng, et al. 2004 Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival Nat Med 10 942 949 15322536 10.1038/nm1093 1:CAS:528:DC%2BD2cXntFSkt7g%3D (Pubitemid 39273735)
16. Y Kiniwa Y Miyahara HY Wang W Peng G Peng, et al. 2007 CD8 + Foxp3 + regulatory T cells mediate immunosuppression in prostate cancer Clin Cancer Res 13 6947 6958 18056169 10.1158/1078-0432.CCR-07-0842 1:CAS:528:DC%2BD2sXhtlyit7fF (Pubitemid 350276874)
17. EY Woo CS Chu TJ Goletz K Schlienger H Yeh, et al. 2001 Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer Cancer Res 61 4766 4772 11406550 1:CAS:528:DC%2BD3MXks1GrtbY%3D (Pubitemid 32691889)
18. AM Wolf D Wolf M Steurer G Gastl E Gunsilius, et al. 2003 Increase of regulatory T cells in the peripheral blood of cancer patients Clin Cancer Res 9 606 612 12576425 (Pubitemid 36182591)
19. Quezada SA, Peggs KS, Simpson TR, Allison JP (2011) Shifting the equilibrium in cancer immunoediting: from tumor tolerance to eradication. Immunol Rev 241:104-118
20. KS Peggs SA Quezada CA Chambers AJ Korman JP Allison 2009 Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies J Exp Med 206 1717 1725 19581407 10.1084/jem.20082492 1:CAS:528:DC%2BD1MXps1enu7w%3D
21. SA Quezada KS Peggs TR Simpson Y Shen DR Littman, et al. 2008 Limited tumor infiltration by activated T effector cells restricts the therapeutic activity of regulatory T cell depletion against established melanoma J Exp Med 205 2125 2138 18725522 10.1084/jem.20080099 1:CAS:528:DC%2BD1cXhtV2is7%2FP
22. SA Quezada KS Peggs MA Curran JP Allison 2006 CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells J Clin Invest 116 1935 1945 16778987 10.1172/JCI27745 1:CAS:528:DC%2BD28XmvV2lurw%3D (Pubitemid 44033317)
23. N Casares L Arribillaga P Sarobe J Dotor A Lopez-Diaz de Cerio, et al. 2003 CD4+/CD25+ regulatory cells inhibit activation of tumor-primed CD4+ T cells with IFN-gamma-dependent antiangiogenic activity, as well as long-lasting tumor immunity elicited by peptide vaccination J Immunol 171 5931 5939 14634104 1:CAS:528:DC%2BD3sXptFOks7k%3D (Pubitemid 37467211)
24. Grimm M, Gasser M, Bueter M, Strehl J, Wang J et al (2010) Evaluation of immunological escape mechanisms in a mouse model of colorectal liver metastases. BMC Cancer 10:82
25. AG Jarnicki J Lysaght S Todryk KH Mills 2006 Suppression of antitumor immunity by IL-10 and TGF-beta-producing T cells infiltrating the growing tumor: influence of tumor environment on the induction of CD4+ and CD8+ regulatory T cells J Immunol 177 896 904 16818744 1:CAS:528:DC%2BD28XmsVartr8%3D (Pubitemid 44036590)
26. ML Disis KH Park 2009 Immunomodulation of breast cancer via tumor antigen specific Th1 Cancer Res Treat 41 117 121 19809560 10.4143/crt.2009.41.3.117
27. ML Penichet PM Challita SU Shin SL Sampogna JD Rosenblatt, et al. 1999 In vivo properties of three human HER2/neu-expressing murine cell lines in immunocompetent mice Lab Anim Sci 49 179 188 10331548 1:STN:280: DyaK1M3mtVeqsw%3D%3D (Pubitemid 29207285)
28. Li Z, Ling L, Liu X, Laus R, Delcayre A (2010) A flow cytometry-based immuno-titration assay for rapid and accurate titer determination of modified vaccinia Ankara virus vectors. J Virol Methods 169:87-94
29. DE Jenkins Y Oei YS Hornig SF Yu J Dusich, et al. 2003 Bioluminescent imaging (BLI) to improve and refine traditional murine models of tumor growth and metastasis Clin Exp Metastasis 20 733 744 14713107 10.1023/B:CLIN. 0000006815.49932.98 1:CAS:528:DC%2BD3sXpsV2ktbw%3D (Pubitemid 38019275)
30. S Sarkar V Kalia WN Haining BT Konieczny S Subramaniam, et al. 2008 Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates J Exp Med 205 625 640 18316415 10.1084/jem.20071641 1:CAS:528:DC%2BD1cXjs1ahtbc%3D (Pubitemid 351439309)
31. AP Kohm JS McMahon JR Podojil WS Begolka M DeGutes, et al. 2006 Cutting Edge: Anti-CD25 monoclonal antibody injection results in the functional inactivation, not depletion, of CD4+CD25+ T regulatory cells J Immunol 176 3301 3305 16517695 1:CAS:528:DC%2BD28XitVSksLw%3D (Pubitemid 43363974)
32. Y Lin TJ Roberts V Sriram S Cho RR Brutkiewicz 2003 Myeloid marker expression on antiviral CD8+ T cells following an acute virus infection Eur J Immunol 33 2736 2743 14515257 10.1002/eji.200324087 1:CAS:528: DC%2BD3sXosFSjsbs%3D (Pubitemid 37337139)
33. M Beyer H Wang N Peters S Doths C Koerner-Rettberg, et al. 2005 The beta2 integrin CD11c distinguishes a subset of cytotoxic pulmonary T cells with potent antiviral effects in vitro and in vivo Respir Res 6 70 16011799 10.1186/1465-9921-6-70 (Pubitemid 41410165)
34. SK Kim KS Schluns L Lefrancois 1999 Induction and visualization of mucosal memory CD8 T cells following systemic virus infection J Immunol 163 4125 4132 10510347 1:CAS:528:DyaK1MXmslels7s%3D (Pubitemid 29474474)
35. YH Kim BK Choi HS Oh WJ Kang RS Mittler, et al. 2009 Mechanisms involved in synergistic anticancer effects of anti-4-1BB and cyclophosphamide therapy Mol Cancer Ther 8 469 478 19190115 10.1158/1535-7163.MCT-08-0993 1:CAS:528:DC%2BD1MXhvFamsbc%3D
36. YH Kim BK Choi KH Kim SW Kang BS Kwon 2008 Combination therapy with cisplatin and anti-4-1BB: synergistic anticancer effects and amelioration of cisplatin-induced nephrotoxicity Cancer Res 68 7264 7269 18794112 10.1158/0008-5472.CAN-08-1365 1:CAS:528:DC%2BD1cXhtFWltLbP
37. BK Choi YH Kim WJ Kang SK Lee KH Kim, et al. 2007 Mechanisms involved in synergistic anticancer immunity of anti-4-1BB and anti-CD4 therapy Cancer Res 67 8891 8899 17875731 10.1158/0008-5472.CAN-07-1056 1:CAS:528:DC%2BD2sXhtVCit7nO (Pubitemid 47437466)
38. Jones E, Golgher D, Simon AK, Dahm-Vicker M, Screaton G et al (2004) The influence of CD25+ cells on the generation of immunity to tumour cell lines in mice. Novartis Found Symp 256:149-152; discussion 152-157, 259-169
39. D Golgher E Jones F Powrie T Elliott A Gallimore 2002 Depletion of CD25+ regulatory cells uncovers immune responses to shared murine tumor rejection antigens Eur J Immunol 32 3267 3275 12555672 10.1002/1521-4141(200211)32: 11<3267::AID-IMMU3267>3.0.CO;2-1 1:CAS:528:DC%2BD38XovF2qs7c%3D (Pubitemid 35414884)
40. E Jones M Dahm-Vicker D Golgher A Gallimore 2003 CD25+ regulatory T cells and tumor immunity Immunol Lett 85 141 143 12527220 10.1016/S0165-2478(02) 00240-7 1:CAS:528:DC%2BD3sXivVersw%3D%3D (Pubitemid 36071568)
41. MA Bookman KM Darcy D Clarke-Pearson RA Boothby IR Horowitz 2003 Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a phase II trial of the Gynecologic Oncology Group J Clin Oncol 21 283 290 12525520 10.1200/JCO.2003.10.104 1:CAS:528: DC%2BD2cXpsVWqs70%3D (Pubitemid 46606157)
42. HJ Stemmler M Schmitt N Harbeck A Willems H Bernhard, et al. 2006 Application of intrathecal trastuzumab (Herceptintrade mark) for treatment of meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer Oncol Rep 15 1373 1377 16596213 1:CAS:528:DC%2BD28XksFKiurY%3D
43. A Natsume R Niwa M Satoh 2009 Improving effector functions of antibodies for cancer treatment: enhancing ADCC and CDC Drug Des Devel Ther 3 7 16 19920917 1:CAS:528:DC%2BD1MXoslSmsLc%3D
44. MR Clark 1997 IgG effector mechanisms Chem Immunol 65 88 110 9018874 10.1159/000319350 1:CAS:528:DyaK2sXnvFyisQ%3D%3D (Pubitemid 27029828)
45. J Galon A Costes F Sanchez-Cabo A Kirilovsky B Mlecnik, et al. 2006 Type, density, and location of immune cells within human colorectal tumors predict clinical outcome Science 313 1960 1964 17008531 10.1126/science.1129139 1:CAS:528:DC%2BD28XhtVSnsrnK (Pubitemid 44498003)
46. B Kreike M van Kouwenhove H Horlings B Weigelt H Peterse, et al. 2007 Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas Breast Cancer Res 9 R65 17910759 10.1186/bcr1771 (Pubitemid 350187481)
47. P Roepman J Jassem EF Smit T Muley J Niklinski, et al. 2009 An immune response enriched 72-gene prognostic profile for early-stage non-small-cell lung cancer Clin Cancer Res 15 284 290 19118056 10.1158/1078-0432.CCR-08-1258 1:CAS:528:DC%2BD1MXhs1ertw%3D%3D
48. L Zhang JR Conejo-Garcia D Katsaros PA Gimotty M Massobrio, et al. 2003 Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer N Engl J Med 348 203 213 12529460 10.1056/NEJMoa020177 1:CAS:528: DC%2BD3sXksVehug%3D%3D (Pubitemid 36077915)