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Erschienen in: Clinical & Experimental Metastasis 3-4/2017

17.04.2017 | Research Paper

LALF32-51-E7 therapeutic vaccine induces antitumor immunity against human papillomavirus type 16 E7-expressing murine tumor metastases in the lungs

verfasst von: Milaid Granadillo, Aileen Batte, Aracelys Blanco, Alain B. Alfonso, José Suárez, Nelson Merino, Rosalina Carballo, Bárbara O. González, Yayrí C. Prieto, Laura Varas, Dayana Soler, Miladys Limonta, Maelys Miyares, Lizet Aldana, Isis Torrens

Erschienen in: Clinical & Experimental Metastasis | Ausgabe 3-4/2017

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Abstract

One important goal of cancer immunotherapy is to prevent and treat tumor metastasis. We have previously reported the significant antitumor effect induced by the immunization with our human papillomavirus therapeutic protein-based vaccine (LALF32-51-E7) without adjuvant and admixed with clinically relevant adjuvants in the subcutaneous TC-1 tumor challenge model. In the present study, we evaluated the efficacy of the above mentioned vaccine formulations in controlling the hematogenous spread of TC-1 tumor cells using a more tumourigenic clone named TC-1* and other intravenous injection site less stressful than the tail vein. We generated a lung metastasis model by injecting TC-1* cells into the retro-orbital venous sinus and this is the first study describing it. Also, this is the first study that demonstrates the efficacy of the immunization with LALF32-51-E7 without adjuvant and admixed with VSSP or Al(OH)3 in controlling metastatic tumors increasing the survival of the mice. Our TC-1 lung metastasis model can be used to test the efficacy of other immunotherapeutic strategies based on E6/E7 antigens.
Literatur
1.
Zurück zum Zitat Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J, Schiffman MH, Moreno V, Kurman R, Shah KV (1995) Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst 87:796–802CrossRefPubMed Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J, Schiffman MH, Moreno V, Kurman R, Shah KV (1995) Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst 87:796–802CrossRefPubMed
2.
Zurück zum Zitat Ikenberg H, Teufel G, Schmitt B, Kommoss F, Stanimirovic B, Pfleiderer A (1993) Human papillomavirus DNA in distant metastases of cervical cancer. Gynecol Oncol 48:56–60CrossRefPubMed Ikenberg H, Teufel G, Schmitt B, Kommoss F, Stanimirovic B, Pfleiderer A (1993) Human papillomavirus DNA in distant metastases of cervical cancer. Gynecol Oncol 48:56–60CrossRefPubMed
3.
Zurück zum Zitat Lancaster WD, Castellano C, Santos C, Delgado G, Kurman RJ, Jenson AB (1986) Human papillomavirus deoxyribonucleic acid in cervical carcinoma from primary and metastatic sites. Am J Obstet Gynecol 154:115–119CrossRefPubMed Lancaster WD, Castellano C, Santos C, Delgado G, Kurman RJ, Jenson AB (1986) Human papillomavirus deoxyribonucleic acid in cervical carcinoma from primary and metastatic sites. Am J Obstet Gynecol 154:115–119CrossRefPubMed
4.
Zurück zum Zitat Baker CC, Phelps WC, Lindgren V, Braun MJ, Gonda MA, Howley PM (1987) Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines. J Virol 61:962–971PubMedPubMedCentral Baker CC, Phelps WC, Lindgren V, Braun MJ, Gonda MA, Howley PM (1987) Structural and transcriptional analysis of human papillomavirus type 16 sequences in cervical carcinoma cell lines. J Virol 61:962–971PubMedPubMedCentral
5.
Zurück zum Zitat Smotkin D, Wettstein FO (1986) Transcription of human papillomavirus type 16 early genes in a cervical cancer and a cancer-derived cell line and identification of the E7 protein. Proc Natl Acad Sci USA 83:4680–4684CrossRefPubMedPubMedCentral Smotkin D, Wettstein FO (1986) Transcription of human papillomavirus type 16 early genes in a cervical cancer and a cancer-derived cell line and identification of the E7 protein. Proc Natl Acad Sci USA 83:4680–4684CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Granadillo M, Vallespi MG, Batte A, Mendoza O, Soria Y, Lugo VM, Torrens I (2011) A novel fusion protein-based vaccine comprising a cell penetrating and immunostimulatory peptide linked to human papillomavirus (HPV) type 16 E7 antigen generates potent immunologic and antitumor responses in mice. Vaccine 29:920–930CrossRefPubMed Granadillo M, Vallespi MG, Batte A, Mendoza O, Soria Y, Lugo VM, Torrens I (2011) A novel fusion protein-based vaccine comprising a cell penetrating and immunostimulatory peptide linked to human papillomavirus (HPV) type 16 E7 antigen generates potent immunologic and antitumor responses in mice. Vaccine 29:920–930CrossRefPubMed
7.
Zurück zum Zitat Granadillo M, Alfonso AB, Vallespi MG, Batte A, Soria Y, Brown E, Limonta M, Prieto YC, Varas L, Torrens I (2016) The LALF32-51 peptide as component of HPV therapeutic vaccine circumvents the alum-mediated inhibition of IL-12 and promotes a Th1 response. J Cell Immunother 2:44–51CrossRef Granadillo M, Alfonso AB, Vallespi MG, Batte A, Soria Y, Brown E, Limonta M, Prieto YC, Varas L, Torrens I (2016) The LALF32-51 peptide as component of HPV therapeutic vaccine circumvents the alum-mediated inhibition of IL-12 and promotes a Th1 response. J Cell Immunother 2:44–51CrossRef
8.
Zurück zum Zitat Chen CH, Wu TC (1998) Experimental vaccine strategies for cancer immunotherapy. J Biomed Sci 5:231–252CrossRefPubMed Chen CH, Wu TC (1998) Experimental vaccine strategies for cancer immunotherapy. J Biomed Sci 5:231–252CrossRefPubMed
9.
Zurück zum Zitat Lin KY, Guarnieri FG, Staveley-O’Carroll KF, Levitsky HI, August JT, Pardoll DM, Wu TC (1996) Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res 56:21–26PubMed Lin KY, Guarnieri FG, Staveley-O’Carroll KF, Levitsky HI, August JT, Pardoll DM, Wu TC (1996) Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res 56:21–26PubMed
10.
Zurück zum Zitat Eisenbach L, Hollander N, Greenfeld L, Yakor H, Segal S, Feldman M (1984) The differential expression of H-2K versus H-2D antigens, distinguishing high-metastatic from low-metastatic clones, is correlated with the immunogenic properties of the tumor cells. Int J Cancer 34:567–573CrossRefPubMed Eisenbach L, Hollander N, Greenfeld L, Yakor H, Segal S, Feldman M (1984) The differential expression of H-2K versus H-2D antigens, distinguishing high-metastatic from low-metastatic clones, is correlated with the immunogenic properties of the tumor cells. Int J Cancer 34:567–573CrossRefPubMed
11.
Zurück zum Zitat Granadillo M, Batte A, Lugo VM, Musacchio A, Bequet-Romero M, Betancourt L, Besada V, Javier L, Molina R, Falcon V, Torrens I (2013) Expression, purification and characterization of a recombinant fusion protein based on the human papillomavirus-16 E7 antigen. Springerplus 2:12CrossRefPubMedPubMedCentral Granadillo M, Batte A, Lugo VM, Musacchio A, Bequet-Romero M, Betancourt L, Besada V, Javier L, Molina R, Falcon V, Torrens I (2013) Expression, purification and characterization of a recombinant fusion protein based on the human papillomavirus-16 E7 antigen. Springerplus 2:12CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Estevez F, Carr A, Solorzano L, Valiente O, Mesa C, Barroso O, Sierra GV, Fernandez LE (1999) Enhancement of the immune response to poorly immunogenic gangliosides after incorporation into very small size proteoliposomes (VSSP). Vaccine 18:190–197CrossRefPubMed Estevez F, Carr A, Solorzano L, Valiente O, Mesa C, Barroso O, Sierra GV, Fernandez LE (1999) Enhancement of the immune response to poorly immunogenic gangliosides after incorporation into very small size proteoliposomes (VSSP). Vaccine 18:190–197CrossRefPubMed
13.
Zurück zum Zitat Ji H, Chang EY, Lin KY, Kurman RJ, Pardoll DM, Wu TC (1998) Antigen-specific immunotherapy for murine lung metastatic tumors expressing human papillomavirus type 16 E7 oncoprotein. Int J Cancer 78:41–45CrossRefPubMed Ji H, Chang EY, Lin KY, Kurman RJ, Pardoll DM, Wu TC (1998) Antigen-specific immunotherapy for murine lung metastatic tumors expressing human papillomavirus type 16 E7 oncoprotein. Int J Cancer 78:41–45CrossRefPubMed
14.
Zurück zum Zitat Pinkerton W, Webber M (1964) A method of injecting small laboratory animals by the ophthalmic plexus route. Proc Soc Exp Biol Med 116:959–961CrossRefPubMed Pinkerton W, Webber M (1964) A method of injecting small laboratory animals by the ophthalmic plexus route. Proc Soc Exp Biol Med 116:959–961CrossRefPubMed
15.
Zurück zum Zitat Bailey M, Engler H, Hunzeker J, Sheridan JF (2003) The hypothalamic-pituitary-adrenal axis and viral infection. Viral Immunol 16:141–157CrossRefPubMed Bailey M, Engler H, Hunzeker J, Sheridan JF (2003) The hypothalamic-pituitary-adrenal axis and viral infection. Viral Immunol 16:141–157CrossRefPubMed
16.
Zurück zum Zitat McEwen BS, Biron CA, Brunson KW, Bulloch K, Chambers WH, Dhabhar FS, Goldfarb RH, Kitson RP, Miller AH, Spencer RL, Weiss JM (1997) The role of adrenocorticoids as modulators of immune function in health and disease: neural, endocrine and immune interactions. Brain Res Brain Res Rev 23:79–133CrossRefPubMed McEwen BS, Biron CA, Brunson KW, Bulloch K, Chambers WH, Dhabhar FS, Goldfarb RH, Kitson RP, Miller AH, Spencer RL, Weiss JM (1997) The role of adrenocorticoids as modulators of immune function in health and disease: neural, endocrine and immune interactions. Brain Res Brain Res Rev 23:79–133CrossRefPubMed
17.
Zurück zum Zitat Steel CD, Stephens AL, Hahto SM, Singletary SJ, Ciavarra RP (2008) Comparison of the lateral tail vein and the retro-orbital venous sinus as routes of intravenous drug delivery in a transgenic mouse model. Lab Anim (NY) 37:26–32CrossRef Steel CD, Stephens AL, Hahto SM, Singletary SJ, Ciavarra RP (2008) Comparison of the lateral tail vein and the retro-orbital venous sinus as routes of intravenous drug delivery in a transgenic mouse model. Lab Anim (NY) 37:26–32CrossRef
Metadaten
Titel
LALF32-51-E7 therapeutic vaccine induces antitumor immunity against human papillomavirus type 16 E7-expressing murine tumor metastases in the lungs
verfasst von
Milaid Granadillo
Aileen Batte
Aracelys Blanco
Alain B. Alfonso
José Suárez
Nelson Merino
Rosalina Carballo
Bárbara O. González
Yayrí C. Prieto
Laura Varas
Dayana Soler
Miladys Limonta
Maelys Miyares
Lizet Aldana
Isis Torrens
Publikationsdatum
17.04.2017
Verlag
Springer Netherlands
Erschienen in
Clinical & Experimental Metastasis / Ausgabe 3-4/2017
Print ISSN: 0262-0898
Elektronische ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-017-9846-x

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