Combination immunotherapy with Survivin and luteinizing hormone-releasing hormone fusion protein in murine breast cancer model
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摘要
AIM To investigate the therapeutic potential of two recombinant proteins, Survivin and luteinizing hormone-releasing hormone (LHRH) fusion protein [LHRH(6 leu)-LTB] for immunotherapy of breast cancer.METHODS Murine 4 T-1 breast cancer model was used to evaluate the efficacy of recombinant proteins in vivo. Twenty four Balb/c mice were divided into 4 groups of 6 mice each. Recombinant Survivin and LHRH fusion protein, alone or in combination, were administered along with immunomodulator Mycobacterium indicus pranii (MIP) in Balb/c mice. Unimmunized or control group mice were administered with phosphate buffer saline. Each group was then challenged with syngeneic 4 T-1 cells to induce the growth of breast tumor. Tumor growth was monitored to evaluate the efficacy of immune-response in preventing the growth of cancer cells.RESULTS Preventive immunization with 20 μg recombinant Survivin and MIP was effective in suppressing growth of 4 T-1 mouse model of breast cancer (P = 0.04) but 50 μg dose was ineffective in suppressing tumor growth. However, combination of Survivin and LHRH fusion protein was more effective in suppressing tumor growth (P = 0.02) as well as metastasis in vivo in comparison to LHRH fusion protein as vaccine antigen alone.CONCLUSION Recombinant Survivin and MIP suppress tumor growth significantly. Combining LHRH fusion protein with Survivin and MIP enhances tumor suppressive effects marginally which provides evidence for recombinant Survivin and LHRH fusion protein as candidates for translating the combination cancer immunotherapy approaches.
AIM To investigate the therapeutic potential of two recombinant proteins, Survivin and luteinizing hormone-releasing hormone (LHRH) fusion protein [LHRH(6 leu)-LTB] for immunotherapy of breast cancer.METHODS Murine 4 T-1 breast cancer model was used to evaluate the efficacy of recombinant proteins in vivo. Twenty four Balb/c mice were divided into 4 groups of 6 mice each. Recombinant Survivin and LHRH fusion protein, alone or in combination, were administered along with immunomodulator Mycobacterium indicus pranii (MIP) in Balb/c mice. Unimmunized or control group mice were administered with phosphate buffer saline. Each group was then challenged with syngeneic 4 T-1 cells to induce the growth of breast tumor. Tumor growth was monitored to evaluate the efficacy of immune-response in preventing the growth of cancer cells.RESULTS Preventive immunization with 20 μg recombinant Survivin and MIP was effective in suppressing growth of 4 T-1 mouse model of breast cancer (P = 0.04) but 50 μg dose was ineffective in suppressing tumor growth. However, combination of Survivin and LHRH fusion protein was more effective in suppressing tumor growth (P = 0.02) as well as metastasis in vivo in comparison to LHRH fusion protein as vaccine antigen alone.CONCLUSION Recombinant Survivin and MIP suppress tumor growth significantly. Combining LHRH fusion protein with Survivin and MIP enhances tumor suppressive effects marginally which provides evidence for recombinant Survivin and LHRH fusion protein as candidates for translating the combination cancer immunotherapy approaches.
AIM To investigate the therapeutic potential of two recombinant proteins, Survivin and luteinizing hormone-releasing hormone (LHRH) fusion protein [LHRH(6 leu)-LTB] for immunotherapy of breast cancer.METHODS Murine 4 T-1 breast cancer model was used to evaluate the efficacy of recombinant proteins in vivo. Twenty four Balb/c mice were divided into 4 groups of 6 mice each. Recombinant Survivin and LHRH fusion protein, alone or in combination, were administered along with immunomodulator Mycobacterium indicus pranii (MIP) in Balb/c mice. Unimmunized or control group mice were administered with phosphate buffer saline. Each group was then challenged with syngeneic 4 T-1 cells to induce the growth of breast tumor. Tumor growth was monitored to evaluate the efficacy of immune-response in preventing the growth of cancer cells.RESULTS Preventive immunization with 20 μg recombinant Survivin and MIP was effective in suppressing growth of 4 T-1 mouse model of breast cancer (P = 0.04) but 50 μg dose was ineffective in suppressing tumor growth. However, combination of Survivin and LHRH fusion protein was more effective in suppressing tumor growth (P = 0.02) as well as metastasis in vivo in comparison to LHRH fusion protein as vaccine antigen alone.CONCLUSION Recombinant Survivin and MIP suppress tumor growth significantly. Combining LHRH fusion protein with Survivin and MIP enhances tumor suppressive effects marginally which provides evidence for recombinant Survivin and LHRH fusion protein as candidates for translating the combination cancer immunotherapy approaches.
引文
1 Zanardi E,Bregni G,de Braud F,Di Cosimo S.Better Together:Targeted Combination Therapies in Breast Cancer.Semin Oncol 2015;42:887-895[PMID:26615133 DOI:10.1053/j.seminoncol.2015.09.029]
2 Biganzoli L,Cufer T,Bruning P,Coleman R,Duchateau L,Calvert AH,Gamucci T,Twelves C,Fargeot P,Epelbaum R.Doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer:The European Organization for Research and Treatment of Cancer 10961 Multicenter Phase III Trial.J Clin Oncol 2002;20:3114-3121[PMID:12118025 DOI:10.1200/JCO.2002.11.005]
3 Jassem J,Pieńkowski T,P?uzańska A,Jelic S,Gorbunova V,Mrsic-Krmpotic Z,Berzins J,Nagykalnai T,Wigler N,Renard J.Doxorubicin and paclitaxel versus fluorouracil,doxorubicin,and cyclophosphamide as first-line therapy for women with metastatic breast cancer:final results of a randomized phase III multicenter trial.J Clin Oncol 2001;19:1707-1715[PMID:11251000 DOI:10.1200/JCO.2001.19.6.1707]
4 Morrissey KM,Yuraszeck TM,Li CC,Zhang Y,Kasichayanula S.Immunotherapy and Novel Combinations in Oncology:Current Landscape,Challenges,and Opportunities.Clin Transl Sci2016;9:89-104[PMID:26924066 DOI:10.1111/cts.12391]
5 Khalil DN,Smith EL,Brentjens RJ,Wolchok JD.The future of cancer treatment:immunomodulation,CARs and combination immunotherapy.Nat Rev Clin Oncol 2016;13:394[PMID:27118494 DOI:10.1038/nrclinonc.2016.65]
6 Wang RF,Wang HY.Immune targets and neoantigens for cancer immunotherapy and precision medicine.Cell Res 2017;27:11-37[PMID:28025978 DOI:10.1038/cr.2016.155]
7 Farkona S,Diamandis EP,Blasutig IM.Cancer immunotherapy:the beginning of the end of cancer?BMC Med 2016;14:73[PMID:27151159 DOI:10.1186/s12916-016-0623-5]
8 Weiner LM,Surana R,Wang S.Monoclonal antibodies:versatile platforms for cancer immunotherapy.Nat Rev Immunol 2010;10:317-327[PMID:20414205 DOI:10.1038/nri2744]
9 Vinay DS,Ryan EP,Pawelec G,Talib WH,Stagg J,Elkord E,Lichtor T,Decker WK,Whelan RL,Kumara HMCS.Immune evasion in cancer:Mechanistic basis and therapeutic strategies.Semin Cancer Biol 2015;35 Suppl:S185-S198[PMID:25818339 DOI:10.1016/j.semcancer.2015.03.004]
10 Cheng KY,Wang ZL,Gu QY,Hao M.Survivin Overexpression Is Associated with Aggressive Clinicopathological Features in Cervical Carcinoma:A Meta-Analysis.PLoS One 2016;11:e0165117[PMID:27764228 DOI:10.1371/journal.pone.0165117]
11 Chuwa AH,Sone K,Oda K,Ikeda Y,Fukuda T,Wada-Hiraike O,Inaba K,Makii C,Takeuchi M,Oki S.Significance of survivin as a prognostic factor and a therapeutic target in endometrial cancer.Gynecol Oncol 2016;141:564-569[PMID:27079211 DOI:10.1016/j.ygyno.2016.04.003]
12 Boullosa LF,Savaliya P,Bonney S,Orchard L,Wickenden H,Lee C,Smits E,Banham AH,Mills KI,Orchard K.Identification of survivin as a promising target for the immunotherapy of adult B-cell acute lymphoblastic leukemia.Oncotarget 2017;9:3853-3866[PMID:29423088 DOI:10.18632/oncotarget.23380]
13 Capper CP,Rae JM,Auchus RJ.The Metabolism,Analysis,and Targeting of Steroid Hormones in Breast and Prostate Cancer.Horm Cancer 2016;7:149-164[PMID:26969590 DOI:10.1007/s12672-016-0259-0]
14 Junco JA,Basalto R,Fuentes F,Bover E,Reyes O,Pimentel E,Calzada L,Castro MD,Arteaga N,López Y.Gonadotrophin releasing hormone-based vaccine,an effective candidate for prostate cancer and other hormone-sensitive neoplasms.Adv Exp Med Biol 2008;617:581-587[PMID:18497085 DOI:10.1007/978-0-387-69080-3_60]
15 Junco JA,Peschke P,Zuna I,Ehemann V,Fuentes F,Bover E,Pimentel E,Basulto R,Reyes O,Calzada L.Immunotherapy of prostate cancer in a murine model using a novel GnRH based vaccine candidate.Vaccine 2007;25:8460-8468[PMID:18022737 DOI:10.1016/j.vaccine.2007.09.033]
16 Garg H,Gupta JC,Talwar GP,Dubey S.Immunotherapy approach with recombinant survivin adjuvanted with alum and MIP suppresses tumor growth in murine model of breast cancer.Prep Biochem Biotechnol 2018;48:264-269[PMID:29355462 DOI:10.1080/10826068.2018.1425710]
17 Taheri A,Dinarvand R,Ahadi F,Khorramizadeh MR,Atyabi F.The in vivo antitumor activity of LHRH targeted methotrexate-human serum albumin nanoparticles in 4T1 tumor-bearing Balb/c mice.Int J Pharm 2012;431:183-189[PMID:22531853 DOI:10.1016/j.ijpharm.2012.04.033]
18 Li M,Tang Z,Zhang Y,Lv S,Li Q,Chen X.Targeted delivery of cisplatin by LHRH-peptide conjugated dextran nanoparticles suppresses breast cancer growth and metastasis.Acta Biomater2015;18:132-143[PMID:25735801 DOI:10.1016/j.actbio.2015.02.022]
19 Gupta JC,Hada RS,Sahai P,Talwar GP.Development of a novel recombinant LHRH fusion protein for therapy of androgen and estrogen dependent cancers.Protein Expr Purif 2017;134:132-138[PMID:28410993 DOI:10.1016/j.pep.2017.04.003]
20 Srinivasan R,Wolchok JD.Tumor antigens for cancer immunotherapy:therapeutic potential of xenogeneic DNA vaccines.J Transl Med 2004;2:12[PMID:15090064 DOI:10.1186/1479-5876-2-12]
21 Ciesielski MJ,Kozbor D,Castanaro CA,Barone TA,Fenstermaker RA.Therapeutic effect of a Thelper cell supported CTL response induced by a survivin peptide vaccine against murine cerebral glioma.Cancer Immunol Immunother 2008;57:1827-1835[PMID:18438666 DOI:10.1007/s00262-008-0510-9]
22 Fenstermaker RA,Ciesielski MJ,Qiu J,Yang N,Frank CL,Lee KP,Mechtler LR,Belal A,Ahluwalia MS,Hutson AD.Clinical study of a survivin long peptide vaccine(SurVaxM)in patients with recurrent malignant glioma.Cancer Immunol Immunother 2016;65:1339-1352[PMID:27576783 DOI:10.1007/s00262-016-1890-x]
23 Yang Z,Wang L,Wang H,Shang X,Niu W,Li J,Wu Y.A novel mimovirus vaccine containing survivin epitope with adjuvant IL-15 induces long-lasting cellular immunity and high antitumor efficiency.Mol Immunol 2008;45:1674-1681[PMID:18035418 DOI:10.1016/j.molimm.2007.10.026]
24 Idenoue S,Hirohashi Y,Torigoe T,Sato Y,Tamura Y,Hariu H,Yamamoto M,Kurotaki T,Tsuruma T,Asanuma H.A potent immunogenic general cancer vaccine that targets survivin,an inhibitor of apoptosis proteins.Clin Cancer Res 2005;11:1474-1482[PMID:15746049 DOI:10.1158/1078-0432.CCR-03-0817]
25 Lennerz V,Gross S,Gallerani E,Sessa C,Mach N,Boehm S,Hess D,von Boehmer L,Knuth A,Ochsenbein AF.Immunologic response to the survivin-derived multi-epitope vaccine EMD640744 in patients with advanced solid tumors.Cancer Immunol Immunother 2014;63:381-394[PMID:24487961 DOI:10.1007/s00262-013-1516-5]
26 Lladser A,Ljungberg K,Tufvesson H,Tazzari M,Roos AK,Quest AF,Kiessling R.Intradermal DNA electroporation induces survivin-specific CTLs,suppresses angiogenesis and confers protection against mouse melanoma.Cancer Immunol Immunother 2010;59:81-92[PMID:19526360 DOI:10.1007/s00262-009-0725-4]
27 Xiang R,Mizutani N,Luo Y,Chiodoni C,Zhou H,Mizutani M,Ba Y,Becker JC,Reisfeld RA.ADNA vaccine targeting survivin combines apoptosis with suppression of angiogenesis in lung tumor eradication.Cancer Res 2005;65:553-561[PMID:15695399]
28 Tanaka T,Kitamura H,Inoue R,Nishida S,Takahashi-Takaya A,Kawami S,Torigoe T,Hirohashi Y,Tsukamoto T,Sato N.Potential survival benefit of anti-apoptosis protein:survivinderived peptide vaccine with and without interferon alpha therapy for patients with advanced or recurrent urothelial cancer--results from phase I clinical trials.Clin Dev Immunol 2013;2013:262967[PMID:24363758 DOI:10.1155/2013/262967]
29 Gotsman I,Israeli D,Alper R,Rabbani E,Engelhardt D,Ilan Y.Induction of immune tolerance toward tumor-associated-antigens enables growth of human hepatoma in mice.Int J Cancer 2002;97:52-57[PMID:11774243 DOI:10.1002/ijc.1576]
30 Suzuki G,Kawase Y,Koyasu S,Yahara I,Kobayashi Y,Schwartz RH.Antigen-induced suppression of the proliferative response of T cell clones.J Immunol 1988;140:1359-1365[PMID:2450125]
31 Michallet MC,Saltel F,Flacher M,Revillard JP,Genestier L.Cathepsin-dependent apoptosis triggered by supraoptimal activation of T lymphocytes:a possible mechanism of high dose tolerance.J Immunol 2004;172:5405-5414[PMID:15100281 DOI:10.4049/jimmunol.172.9.5405]
32 Ikeda H,Old LJ,Schreiber RD.The roles of IFN gamma in protection against tumor development and cancer immunoediting.Cytokine Growth Factor Rev 2002;13:95-109[PMID:11900986 DOI:10.1016/S1359-6101(01)00038-7]
33 Blankenstein T,Qin Z.The role of IFN-gamma in tumor transplantation immunity and inhibition of chemical carcinogenesis.Curr Opin Immunol 2003;15:148-154[PMID:12633663 DOI:10.1016/S0952-7915(03)00007-4]
34 Dunn GP,Old LJ,Schreiber RD.The immunobiology of cancer immunosurveillance and immunoediting.Immunity 2004;21:137-148[PMID:15308095 DOI:10.1016/j.immuni.2004.07.017]
35 Tsou P,Katayama H,Ostrin EJ,Hanash SM.The Emerging Role of B Cells in Tumor Immunity.Cancer Res 2016;76:5597-5601[PMID:27634765 DOI:10.1158/0008-5472.CAN-16-0431]
36 Fenstermaker RA,Figel SA,Qiu J,Barone TA,Dharma SS,Winograd EK,Galbo PM,Wiltsie LM,Ciesielski MJ.Survivin Monoclonal Antibodies Detect Survivin Cell Surface Expression and Inhibit Tumor Growth In Vivo.Clin Cancer Res 2018;24:2642-2652[PMID:29540489 DOI:10.1158/1078-0432.CCR-17-2778]
37 Goel S,Sharma R,Hamilton A,Beith J.LHRH agonists for adjuvant therapy of early breast cancer in premenopausal women.Cochrane Database Syst Rev 2009;4:CD004562[PMID:19821328DOI:10.1002/14651858.CD004562.pub4]
38 Calderon LE,Keeling JK,Rollins J,Black CA,Collins K,Arnold N,Vance DE,Ndinguri MW.PtMal-LHRH,a Newly Synthesized Compound Attenuating Breast Cancer Tumor Growth and Metastasis by Targeting Overexpression of the LHRH Receptor.Bioconjug Chem 2017;28:461-470[PMID:27997127 DOI:10.1021/acs.bioconjchem.6b00610]
2 Biganzoli L,Cufer T,Bruning P,Coleman R,Duchateau L,Calvert AH,Gamucci T,Twelves C,Fargeot P,Epelbaum R.Doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer:The European Organization for Research and Treatment of Cancer 10961 Multicenter Phase III Trial.J Clin Oncol 2002;20:3114-3121[PMID:12118025 DOI:10.1200/JCO.2002.11.005]
3 Jassem J,Pieńkowski T,P?uzańska A,Jelic S,Gorbunova V,Mrsic-Krmpotic Z,Berzins J,Nagykalnai T,Wigler N,Renard J.Doxorubicin and paclitaxel versus fluorouracil,doxorubicin,and cyclophosphamide as first-line therapy for women with metastatic breast cancer:final results of a randomized phase III multicenter trial.J Clin Oncol 2001;19:1707-1715[PMID:11251000 DOI:10.1200/JCO.2001.19.6.1707]
4 Morrissey KM,Yuraszeck TM,Li CC,Zhang Y,Kasichayanula S.Immunotherapy and Novel Combinations in Oncology:Current Landscape,Challenges,and Opportunities.Clin Transl Sci2016;9:89-104[PMID:26924066 DOI:10.1111/cts.12391]
5 Khalil DN,Smith EL,Brentjens RJ,Wolchok JD.The future of cancer treatment:immunomodulation,CARs and combination immunotherapy.Nat Rev Clin Oncol 2016;13:394[PMID:27118494 DOI:10.1038/nrclinonc.2016.65]
6 Wang RF,Wang HY.Immune targets and neoantigens for cancer immunotherapy and precision medicine.Cell Res 2017;27:11-37[PMID:28025978 DOI:10.1038/cr.2016.155]
7 Farkona S,Diamandis EP,Blasutig IM.Cancer immunotherapy:the beginning of the end of cancer?BMC Med 2016;14:73[PMID:27151159 DOI:10.1186/s12916-016-0623-5]
8 Weiner LM,Surana R,Wang S.Monoclonal antibodies:versatile platforms for cancer immunotherapy.Nat Rev Immunol 2010;10:317-327[PMID:20414205 DOI:10.1038/nri2744]
9 Vinay DS,Ryan EP,Pawelec G,Talib WH,Stagg J,Elkord E,Lichtor T,Decker WK,Whelan RL,Kumara HMCS.Immune evasion in cancer:Mechanistic basis and therapeutic strategies.Semin Cancer Biol 2015;35 Suppl:S185-S198[PMID:25818339 DOI:10.1016/j.semcancer.2015.03.004]
10 Cheng KY,Wang ZL,Gu QY,Hao M.Survivin Overexpression Is Associated with Aggressive Clinicopathological Features in Cervical Carcinoma:A Meta-Analysis.PLoS One 2016;11:e0165117[PMID:27764228 DOI:10.1371/journal.pone.0165117]
11 Chuwa AH,Sone K,Oda K,Ikeda Y,Fukuda T,Wada-Hiraike O,Inaba K,Makii C,Takeuchi M,Oki S.Significance of survivin as a prognostic factor and a therapeutic target in endometrial cancer.Gynecol Oncol 2016;141:564-569[PMID:27079211 DOI:10.1016/j.ygyno.2016.04.003]
12 Boullosa LF,Savaliya P,Bonney S,Orchard L,Wickenden H,Lee C,Smits E,Banham AH,Mills KI,Orchard K.Identification of survivin as a promising target for the immunotherapy of adult B-cell acute lymphoblastic leukemia.Oncotarget 2017;9:3853-3866[PMID:29423088 DOI:10.18632/oncotarget.23380]
13 Capper CP,Rae JM,Auchus RJ.The Metabolism,Analysis,and Targeting of Steroid Hormones in Breast and Prostate Cancer.Horm Cancer 2016;7:149-164[PMID:26969590 DOI:10.1007/s12672-016-0259-0]
14 Junco JA,Basalto R,Fuentes F,Bover E,Reyes O,Pimentel E,Calzada L,Castro MD,Arteaga N,López Y.Gonadotrophin releasing hormone-based vaccine,an effective candidate for prostate cancer and other hormone-sensitive neoplasms.Adv Exp Med Biol 2008;617:581-587[PMID:18497085 DOI:10.1007/978-0-387-69080-3_60]
15 Junco JA,Peschke P,Zuna I,Ehemann V,Fuentes F,Bover E,Pimentel E,Basulto R,Reyes O,Calzada L.Immunotherapy of prostate cancer in a murine model using a novel GnRH based vaccine candidate.Vaccine 2007;25:8460-8468[PMID:18022737 DOI:10.1016/j.vaccine.2007.09.033]
16 Garg H,Gupta JC,Talwar GP,Dubey S.Immunotherapy approach with recombinant survivin adjuvanted with alum and MIP suppresses tumor growth in murine model of breast cancer.Prep Biochem Biotechnol 2018;48:264-269[PMID:29355462 DOI:10.1080/10826068.2018.1425710]
17 Taheri A,Dinarvand R,Ahadi F,Khorramizadeh MR,Atyabi F.The in vivo antitumor activity of LHRH targeted methotrexate-human serum albumin nanoparticles in 4T1 tumor-bearing Balb/c mice.Int J Pharm 2012;431:183-189[PMID:22531853 DOI:10.1016/j.ijpharm.2012.04.033]
18 Li M,Tang Z,Zhang Y,Lv S,Li Q,Chen X.Targeted delivery of cisplatin by LHRH-peptide conjugated dextran nanoparticles suppresses breast cancer growth and metastasis.Acta Biomater2015;18:132-143[PMID:25735801 DOI:10.1016/j.actbio.2015.02.022]
19 Gupta JC,Hada RS,Sahai P,Talwar GP.Development of a novel recombinant LHRH fusion protein for therapy of androgen and estrogen dependent cancers.Protein Expr Purif 2017;134:132-138[PMID:28410993 DOI:10.1016/j.pep.2017.04.003]
20 Srinivasan R,Wolchok JD.Tumor antigens for cancer immunotherapy:therapeutic potential of xenogeneic DNA vaccines.J Transl Med 2004;2:12[PMID:15090064 DOI:10.1186/1479-5876-2-12]
21 Ciesielski MJ,Kozbor D,Castanaro CA,Barone TA,Fenstermaker RA.Therapeutic effect of a Thelper cell supported CTL response induced by a survivin peptide vaccine against murine cerebral glioma.Cancer Immunol Immunother 2008;57:1827-1835[PMID:18438666 DOI:10.1007/s00262-008-0510-9]
22 Fenstermaker RA,Ciesielski MJ,Qiu J,Yang N,Frank CL,Lee KP,Mechtler LR,Belal A,Ahluwalia MS,Hutson AD.Clinical study of a survivin long peptide vaccine(SurVaxM)in patients with recurrent malignant glioma.Cancer Immunol Immunother 2016;65:1339-1352[PMID:27576783 DOI:10.1007/s00262-016-1890-x]
23 Yang Z,Wang L,Wang H,Shang X,Niu W,Li J,Wu Y.A novel mimovirus vaccine containing survivin epitope with adjuvant IL-15 induces long-lasting cellular immunity and high antitumor efficiency.Mol Immunol 2008;45:1674-1681[PMID:18035418 DOI:10.1016/j.molimm.2007.10.026]
24 Idenoue S,Hirohashi Y,Torigoe T,Sato Y,Tamura Y,Hariu H,Yamamoto M,Kurotaki T,Tsuruma T,Asanuma H.A potent immunogenic general cancer vaccine that targets survivin,an inhibitor of apoptosis proteins.Clin Cancer Res 2005;11:1474-1482[PMID:15746049 DOI:10.1158/1078-0432.CCR-03-0817]
25 Lennerz V,Gross S,Gallerani E,Sessa C,Mach N,Boehm S,Hess D,von Boehmer L,Knuth A,Ochsenbein AF.Immunologic response to the survivin-derived multi-epitope vaccine EMD640744 in patients with advanced solid tumors.Cancer Immunol Immunother 2014;63:381-394[PMID:24487961 DOI:10.1007/s00262-013-1516-5]
26 Lladser A,Ljungberg K,Tufvesson H,Tazzari M,Roos AK,Quest AF,Kiessling R.Intradermal DNA electroporation induces survivin-specific CTLs,suppresses angiogenesis and confers protection against mouse melanoma.Cancer Immunol Immunother 2010;59:81-92[PMID:19526360 DOI:10.1007/s00262-009-0725-4]
27 Xiang R,Mizutani N,Luo Y,Chiodoni C,Zhou H,Mizutani M,Ba Y,Becker JC,Reisfeld RA.ADNA vaccine targeting survivin combines apoptosis with suppression of angiogenesis in lung tumor eradication.Cancer Res 2005;65:553-561[PMID:15695399]
28 Tanaka T,Kitamura H,Inoue R,Nishida S,Takahashi-Takaya A,Kawami S,Torigoe T,Hirohashi Y,Tsukamoto T,Sato N.Potential survival benefit of anti-apoptosis protein:survivinderived peptide vaccine with and without interferon alpha therapy for patients with advanced or recurrent urothelial cancer--results from phase I clinical trials.Clin Dev Immunol 2013;2013:262967[PMID:24363758 DOI:10.1155/2013/262967]
29 Gotsman I,Israeli D,Alper R,Rabbani E,Engelhardt D,Ilan Y.Induction of immune tolerance toward tumor-associated-antigens enables growth of human hepatoma in mice.Int J Cancer 2002;97:52-57[PMID:11774243 DOI:10.1002/ijc.1576]
30 Suzuki G,Kawase Y,Koyasu S,Yahara I,Kobayashi Y,Schwartz RH.Antigen-induced suppression of the proliferative response of T cell clones.J Immunol 1988;140:1359-1365[PMID:2450125]
31 Michallet MC,Saltel F,Flacher M,Revillard JP,Genestier L.Cathepsin-dependent apoptosis triggered by supraoptimal activation of T lymphocytes:a possible mechanism of high dose tolerance.J Immunol 2004;172:5405-5414[PMID:15100281 DOI:10.4049/jimmunol.172.9.5405]
32 Ikeda H,Old LJ,Schreiber RD.The roles of IFN gamma in protection against tumor development and cancer immunoediting.Cytokine Growth Factor Rev 2002;13:95-109[PMID:11900986 DOI:10.1016/S1359-6101(01)00038-7]
33 Blankenstein T,Qin Z.The role of IFN-gamma in tumor transplantation immunity and inhibition of chemical carcinogenesis.Curr Opin Immunol 2003;15:148-154[PMID:12633663 DOI:10.1016/S0952-7915(03)00007-4]
34 Dunn GP,Old LJ,Schreiber RD.The immunobiology of cancer immunosurveillance and immunoediting.Immunity 2004;21:137-148[PMID:15308095 DOI:10.1016/j.immuni.2004.07.017]
35 Tsou P,Katayama H,Ostrin EJ,Hanash SM.The Emerging Role of B Cells in Tumor Immunity.Cancer Res 2016;76:5597-5601[PMID:27634765 DOI:10.1158/0008-5472.CAN-16-0431]
36 Fenstermaker RA,Figel SA,Qiu J,Barone TA,Dharma SS,Winograd EK,Galbo PM,Wiltsie LM,Ciesielski MJ.Survivin Monoclonal Antibodies Detect Survivin Cell Surface Expression and Inhibit Tumor Growth In Vivo.Clin Cancer Res 2018;24:2642-2652[PMID:29540489 DOI:10.1158/1078-0432.CCR-17-2778]
37 Goel S,Sharma R,Hamilton A,Beith J.LHRH agonists for adjuvant therapy of early breast cancer in premenopausal women.Cochrane Database Syst Rev 2009;4:CD004562[PMID:19821328DOI:10.1002/14651858.CD004562.pub4]
38 Calderon LE,Keeling JK,Rollins J,Black CA,Collins K,Arnold N,Vance DE,Ndinguri MW.PtMal-LHRH,a Newly Synthesized Compound Attenuating Breast Cancer Tumor Growth and Metastasis by Targeting Overexpression of the LHRH Receptor.Bioconjug Chem 2017;28:461-470[PMID:27997127 DOI:10.1021/acs.bioconjchem.6b00610]