id:"swepub:oai:DiVA.org:uu-231464"
Sökning: id:"swepub:oai:DiVA.org:uu-231464" > Local CTLA4 blockad...
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 05048naa a2200505 4500 | |
| 001 | oai:DiVA.org:uu-231464 | |
| 003 | SwePub | |
| 008 | 140908s2014 | |||||||||||000 ||eng| | |
| 009 | oai:lup.lub.lu.se:d728aade-3df8-44d1-91fb-e8f6b2c02c05 | |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2314642 URI |
| 024 | 7 | a https://doi.org/10.4161/onci.276142 DOI |
| 024 | 7 | a https://lup.lub.lu.se/record/44308272 URI |
| 040 | a (SwePub)uud (SwePub)lu | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Sandin, Linda C.u Uppsala universitet,Klinisk immunologi4 aut0 (Swepub:uu)lingu457 |
| 245 | 1 0 | a Local CTLA4 blockade effectively restrains experimental pancreatic adenocarcinoma growth in vivo |
| 264 | c 2014-01-16 | |
| 264 | 1 | b Informa UK Limited,c 2014 |
| 338 | a print2 rdacarrier | |
| 520 | a Antibody-mediated blockade of CTLA4 has been shown to be effective in treating a select group of patients with late-stage melanoma. The precise mechanism underlying the clinical activity of CTLA4 immunotherapy is poorly understood, although recent experimental findings indicate that antibody-mediated depletion of regulatory T cells (Tregs) in the tumor microenvironment plays a key role in efficacious antitumor responses. In the current study, we used an experimental model of pancreatic adenocarcinoma to compare the antitumor efficacy of peritumoral low-dose anti-CTLA4 monoclonal antibody (mAb) administration to that of a commonly utilized systemic high-dose anti-CTLA4 regimen. We selected pancreatic adenocarcinoma as it presents a particular challenge to clinicians due to its aggressive behavior, metastatic spread and limited treatment options. Furthermore, Fc gamma receptor (Fc gamma R)-dense myeloid cells commonly infiltrate pancreatic tumors, such that these tumor types exhibit increased susceptibility to CTLA4 antibody-targeted Treg depletion via antibody-dependent cell-mediated cytotoxicity (ADCC). Locally administered anti-CTLA4 mAb effectively reduced tumor growth at a low dose and no additional anti-tumor effects were apparent when increasing the dose or number of injections. No significant difference in overall survival was seen when comparing locally administered low-dose with standard systemic high-dose CTLA4 blockade therapy, and both delivery routes led to increased tumor-infiltrating effector T cells and reduced Treg cells. As opposed to low-dose peritumoral treatment, high-dose systemic therapy stimulated the accumulation of Tregs in secondary lymphoid organs, an effect that could potentially counteract the antitumor immunotherapeutic benefit of CTLA4 blockade. Our study confirms previous findings that local administration of low-dose anti-CTLA4 antibody generates sustained antitumor effects and provides rationale to devise ultrasound-guided intratumoral anti-CTLA4 antibody injection regimens to treat patients with pancreatic adenocarcinoma and other types of solid tumors. In support, clinical relevancy could include reduced immune-related adverse events by limiting systemic antibody spread to immune cell-dense organs. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Immunologi inom det medicinska området0 (SwePub)301102 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Immunology in the medical area0 (SwePub)301102 hsv//eng |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng |
| 653 | a local therapy | |
| 653 | a anti-CTLA4 | |
| 653 | a checkpoint blockade | |
| 653 | a immunotherapy | |
| 653 | a pancreatic cancer | |
| 700 | 1 | a Eriksson, Fredriku Uppsala universitet,Klinisk immunologi4 aut0 (Swepub:uu)freer194 |
| 700 | 1 | a Ellmark, Peteru Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH4 aut0 (Swepub:lu)immt-pel |
| 700 | 1 | a Loskog, Angelica S. I.u Uppsala universitet,Klinisk immunologi4 aut0 (Swepub:uu)angelosk |
| 700 | 1 | a Tötterman, Thomas H.u Uppsala universitet,Klinisk immunologi4 aut0 (Swepub:uu)thomtott |
| 700 | 1 | a Mangsbo, Sara M.u Uppsala universitet,Klinisk immunologi4 aut0 (Swepub:uu)saman132 |
| 710 | 2 | a Uppsala universitetb Klinisk immunologi4 org |
| 773 | 0 | t Oncoimmunologyd : Informa UK Limitedg 3:1, s. e2761-q 3:1<e2761-x 2162-4011x 2162-402X |
| 856 | 4 | u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962508/y Free fulltext |
| 856 | 4 | u https://www.tandfonline.com/doi/pdf/10.4161/onci.27614?needAccess=true |
| 856 | 4 | u http://dx.doi.org/10.4161/onci.27614y FULLTEXT |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-231464 |
| 856 | 4 8 | u https://doi.org/10.4161/onci.27614 |
| 856 | 4 8 | u https://lup.lub.lu.se/record/4430827 |
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