Sökning: id:"swepub:oai:gup.ub.gu.se/255700" >
Intratumorally inje...
Intratumorally injected pro-inflammatory allogeneic dendritic cells as immune enhancers: a first-in-human study in unfavourable risk patients with metastatic renal cell carcinoma
-
- Laurell, Anna (författare)
- Uppsala universitet,Experimentell och klinisk onkologi
-
- Lönnemark, Maria (författare)
- Uppsala universitet,Radiologi
-
- Brekkan, Einar (författare)
- Uppsala universitet,Urologkirurgi
-
visa fler...
-
- Magnusson, Anders, 1947- (författare)
- Uppsala universitet,Radiologi
-
- Tolf, Anna (författare)
- Uppsala universitet,Klinisk och experimentell patologi
-
- Wallgren, A. C. (författare)
- Karolinska Inst, Dept Pathol, Stockholm, Sweden
-
- Andersson, Bengt A., 1952 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology,Univ Gothenburg, Dept Microbiol & Immunol, Gothenburg, Sweden
-
- Adamson, L. (författare)
- Karolinska Institutet
-
- Kiessling, R. (författare)
- Karolinska Institutet
-
- Karlsson-Parra, Alex (författare)
- Uppsala universitet,Klinisk immunologi,Immunicum AB, Gothenburg, Sweden
-
visa färre...
-
(creator_code:org_t)
- 2017-06-20
- 2017
- Engelska.
-
Ingår i: Journal for Immunotherapy of Cancer. - : BMJ. - 2051-1426. ; 5
- Relaterad länk:
-
https://jitc.biomedc...
-
visa fler...
-
https://doi.org/10.1...
-
https://uu.diva-port... (primary) (Raw object)
-
https://gup.ub.gu.se...
-
https://doi.org/10.1...
-
https://urn.kb.se/re...
-
http://kipublication...
-
visa färre...
Abstract
Ämnesord
Stäng
- Background: Accumulating pre-clinical data indicate that the efficient induction of antigen-specific cytotoxic CD8+ T cells characterizing viral infections is caused by cross-priming where initially infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected bystander DCs. Our DC-based immunotherapy concept is guided by such bystander view and accordingly, we have developed a cellular adjuvant consisting of pre-activated allogeneic DCs producing high levels of DC-recruiting and DC-activating factors. This concept doesn't require MHC-compatibility between injected cells and the patient and therefore introduces the possibility of using pre-produced and freeze-stored DCs from healthy blood donors as an off-the-shelf immune enhancer. The use of MHC-incompatible allogeneic DCs will further induce a local rejection process at the injection site that is expected to further enhance recruitment and maturation of endogenous bystander DCs. Methods: Twelve intermediate and poor risk patients with newly diagnosed metastatic renal cell carcinoma (mRCC) where included in a phase I/II study. Pro-inflammatory allogeneic DCs were produced from a leukapheresis product collected from one healthy blood donor and subsequently deep-frozen. A dose of 5-20 x 106 DCs (INTUVAX) was injected into the renal tumor twice with 2 weeks interval before planned nephrectomy and subsequent standard of care. Results: No INTUVAX-related severe adverse events were observed. A massive infiltration of CD8+ T cells was found in 5 out of 12 removed kidney tumors. No objective tumor response was observed and 6 out of 11 evaluable patients have subsequently received additional treatment with standard tyrosine kinase inhibitors (TKI). Three of these 6 patients experienced an objective tumor response including one sunitinib-treated patient who responded with a complete and durable regression of 4 brain metastases. Median overall survival (mOS) is still not reached (currently 42.5 months) but has already passed historical mOS in patients with unfavourable risk mRCC on standard TKI therapy. Conclusions: Our findings indicate that intratumoral administration of proinflammatory allogeneic DCs induces an antitumor immune response that may prolong survival in unfavourable risk mRCC-patients given subsequent standard of care. A randomized, multi-center, phase II mRCC trial (MERECA) with INTUVAX in conjuction with sunitinib has been initiated.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Metastatic renal cell carcinoma
- Phase I/II study
- Intratumoral administration
- Vaccine
- Allogeneic dendritic cells
- Anti-tumor response
- INTUVAX
- Sunitinib
- cancer-immunotherapy
- solid tumors
- t-cells
- sunitinib
- expression
- blockade
- melanoma
- virus
- activation
- therapies
- Oncology
- Allogeneic dendritic cells
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Laurell, Anna
-
Lönnemark, Maria
-
Brekkan, Einar
-
Magnusson, Ander ...
-
Tolf, Anna
-
Wallgren, A. C.
-
visa fler...
-
Andersson, Bengt ...
-
Adamson, L.
-
Kiessling, R.
-
Karlsson-Parra, ...
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Cancer och onkol ...
- Artiklar i publikationen
-
Journal for Immu ...
- Av lärosätet
-
Göteborgs universitet
-
Uppsala universitet
-
Karolinska Institutet