Routes of delivery for CpG and anti-CD137 for the treatment of orthotopic kidney tumors in mice.

We have found previously that the tumor cell lines, Renca (a renal cancer) and MC38 (a colon tumor) which had been injected subcutaneously in mice, could be successfully treated with a combination therapy of an oligodeoxynucleotide (CpG1826) (injected intratumorally) and anti-CD137 antibody (injecte...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jennifer A Westwood, Titaina C U Potdevin Hunnam, Hollie J Pegram, Rodney J Hicks, Phillip K Darcy, Michael H Kershaw
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fd5b3730ab394de5b229a7bcf7cbde95
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:fd5b3730ab394de5b229a7bcf7cbde95
record_format	dspace
spelling	oai:doaj.org-article:fd5b3730ab394de5b229a7bcf7cbde952021-11-18T08:21:03ZRoutes of delivery for CpG and anti-CD137 for the treatment of orthotopic kidney tumors in mice.1932-620310.1371/journal.pone.0095847https://doaj.org/article/fd5b3730ab394de5b229a7bcf7cbde952014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24788789/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203We have found previously that the tumor cell lines, Renca (a renal cancer) and MC38 (a colon tumor) which had been injected subcutaneously in mice, could be successfully treated with a combination therapy of an oligodeoxynucleotide (CpG1826) (injected intratumorally) and anti-CD137 antibody (injected intraperitoneally). Thus the combination treatment was expected to initiate a "danger" signal via TLR9 on immune cells, and the anti-CD137 was expected to further activate T cells. In the present study, we found that several other tumor types injected subcutaneously could also be successfully treated with this combination therapy. In addition, we wished to determine if the treatment could work as effectively in an orthotopic metastatic model, which is more physiologically relevant to cancer in humans. Renca was selected as we were familiar with injecting this orthotopically into the outer cortex of the kidney in mice, and it spontaneously metastasizes to lung and abdominal sites. We tested various routes of delivery of CpG combined with intraperitoneal delivery of anti-CD137. Orthotopic tumors were injected with CpG intratumorally, using ultrasound-guided delivery on multiple occasions, combined with anti-CD137 intraperitoneally. A reduction in primary tumor size was observed following intratumoral injection of CpG compared to other treatments. We found that there was a statistically significant increase in survival of mice with orthotopic Renca tumor following intratumoral injection of CpG. However, we determined that the most effective route of delivery of CpG was intravenous, which led to further significantly enhanced survival of mice when combined with anti-CD137 intraperitoneally, likely due to inhibition of metastatic disease. Our data supports future development of this combination therapy for cancer.Jennifer A WestwoodTitaina C U Potdevin HunnamHollie J PegramRodney J HicksPhillip K DarcyMichael H KershawPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e95847 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jennifer A Westwood Titaina C U Potdevin Hunnam Hollie J Pegram Rodney J Hicks Phillip K Darcy Michael H Kershaw Routes of delivery for CpG and anti-CD137 for the treatment of orthotopic kidney tumors in mice.
description	We have found previously that the tumor cell lines, Renca (a renal cancer) and MC38 (a colon tumor) which had been injected subcutaneously in mice, could be successfully treated with a combination therapy of an oligodeoxynucleotide (CpG1826) (injected intratumorally) and anti-CD137 antibody (injected intraperitoneally). Thus the combination treatment was expected to initiate a "danger" signal via TLR9 on immune cells, and the anti-CD137 was expected to further activate T cells. In the present study, we found that several other tumor types injected subcutaneously could also be successfully treated with this combination therapy. In addition, we wished to determine if the treatment could work as effectively in an orthotopic metastatic model, which is more physiologically relevant to cancer in humans. Renca was selected as we were familiar with injecting this orthotopically into the outer cortex of the kidney in mice, and it spontaneously metastasizes to lung and abdominal sites. We tested various routes of delivery of CpG combined with intraperitoneal delivery of anti-CD137. Orthotopic tumors were injected with CpG intratumorally, using ultrasound-guided delivery on multiple occasions, combined with anti-CD137 intraperitoneally. A reduction in primary tumor size was observed following intratumoral injection of CpG compared to other treatments. We found that there was a statistically significant increase in survival of mice with orthotopic Renca tumor following intratumoral injection of CpG. However, we determined that the most effective route of delivery of CpG was intravenous, which led to further significantly enhanced survival of mice when combined with anti-CD137 intraperitoneally, likely due to inhibition of metastatic disease. Our data supports future development of this combination therapy for cancer.
format	article
author	Jennifer A Westwood Titaina C U Potdevin Hunnam Hollie J Pegram Rodney J Hicks Phillip K Darcy Michael H Kershaw
author_facet	Jennifer A Westwood Titaina C U Potdevin Hunnam Hollie J Pegram Rodney J Hicks Phillip K Darcy Michael H Kershaw
author_sort	Jennifer A Westwood
title	Routes of delivery for CpG and anti-CD137 for the treatment of orthotopic kidney tumors in mice.
title_short	Routes of delivery for CpG and anti-CD137 for the treatment of orthotopic kidney tumors in mice.
title_full	Routes of delivery for CpG and anti-CD137 for the treatment of orthotopic kidney tumors in mice.
title_fullStr	Routes of delivery for CpG and anti-CD137 for the treatment of orthotopic kidney tumors in mice.
title_full_unstemmed	Routes of delivery for CpG and anti-CD137 for the treatment of orthotopic kidney tumors in mice.
title_sort	routes of delivery for cpg and anti-cd137 for the treatment of orthotopic kidney tumors in mice.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/fd5b3730ab394de5b229a7bcf7cbde95
work_keys_str_mv	AT jenniferawestwood routesofdeliveryforcpgandanticd137forthetreatmentoforthotopickidneytumorsinmice AT titainacupotdevinhunnam routesofdeliveryforcpgandanticd137forthetreatmentoforthotopickidneytumorsinmice AT holliejpegram routesofdeliveryforcpgandanticd137forthetreatmentoforthotopickidneytumorsinmice AT rodneyjhicks routesofdeliveryforcpgandanticd137forthetreatmentoforthotopickidneytumorsinmice AT phillipkdarcy routesofdeliveryforcpgandanticd137forthetreatmentoforthotopickidneytumorsinmice AT michaelhkershaw routesofdeliveryforcpgandanticd137forthetreatmentoforthotopickidneytumorsinmice
_version_	1718421900674203648

Routes of delivery for CpG and anti-CD137 for the treatment of orthotopic kidney tumors in mice.

Ejemplares similares