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- Fröbom, Robin, et al.
(författare)
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Phase I trial evaluating safety and efficacy of intratumorally administered inflammatory allogeneic dendritic cells (ilixadencel) in advanced gastrointestinal stromal tumors
- 2020
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Ingår i: Cancer Immunology and Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 69:11, s. 2393-2401
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe majority of patients with advanced gastrointestinal stromal tumor (GIST) develop resistance to imatinib, and subsequent treatments have limited efficacy. Ilixadencel (allogeneic inflammatory dendritic cells) is a cell-based immune primer injected intratumorally that previously has been clinically investigated in metastatic renal cell carcinoma and hepatocellular carcinoma.MethodsThe trial was a single arm phase I trial assessing safety and efficacy of ilixadencel in subjects with progressing advanced/metastatic GIST despite ongoing treatment with second or later lines of tyrosine kinase inhibitors (TKI). Three patients were progressing while on sunitinib (second line), one on regorafenib (third line), and two on pazopanib (fourth line). TKI treatment was maintained throughout, while two intratumoral injections of ilixadencel (10 × 106 viable and HLA-DR expressing cells per dose) were administered.ResultsNo severe adverse events were found to be related to ilixadencel administration. Four patients showed continued tumor progression at 3 months per RECIST 1.1 and Choi criteria. One patient (on third line regorafenib) had stable disease for 9 months and another patient (on second line sunitinib) had stable disease at end of study (12 months) as per RECIST 1.1. These two patients developed a partial response as per Choi criteria with a duration of 3 and 6 months, respectively. The median progression-free survival (PFS) was 4.0 months.ConclusionIlixadencel treatment presented an acceptable safety profile among advanced GIST patients who developed resistance to TKI. Encouraging radiological tumor responses were detected in 33% of treated patients, supporting further investigation.
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| 2. |
- Karlsson-Parra, Alex, et al.
(författare)
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Ilixadencel - an Allogeneic Cell-Based Anticancer Immune Primer for Intratumoral Administration
- 2018
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 35:8
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Forskningsöversikt (refereegranskat)abstract
- Intratumoral administration of an immune primer is a therapeutic vaccine strategy aimed to trigger dendritic cell (DC)-mediated cross-presentation of cell-associated tumor antigens to cytotoxic CD8(+) T cells without the need for tumor antigen characterization. The prevailing view is that these cross-presenting DCs have to be directly activated by pathogen-associated molecular patterns (PAMPS), including Toll-like receptor ligands or live microbial agents like oncolytic viruses. Emerging data are however challenging this view, indicating that the cross-presenting machinery in DCs is suboptimally activated by direct PAMP recognition, and that endogenous inflammatory factors are the main drivers of DC-mediated cross-presentation within the tumor. Here we present preclinical mode of action data, CMC and regulatory data, as well as initial clinical data on ilixadencel. This cell-based drug product is an off-the-shelf immune primer, consisting of pro-inflammatory allogeneic DCs secreting high amounts of pro-inflammatory chemokines and cytokines at the time of intratumoral administration. The mechanism of action of ilixadencel is to induce recruitment and activation of endogenous immune cells, including NK cells that subsequently promotes cross-presentation of cell-associated tumor antigens by co-recruited DCs.
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| 3. |
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| 4. |
- Rizell, Magnus, et al.
(författare)
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Phase 1 Trial With the Cell-Based Immune Primer Ilixadencel, Alone, and Combined With Sorafenib, in Advanced Hepatocellular Carcinoma
- 2019
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 9, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Several lines of evidence support immunotherapy in hepatocellular carcinoma (HCC). We have shown that intratumoral injections of the immune primer ilixadencel (pro-inflammatory allogeneic dendritic cells) are safe in renal-cell carcinoma. Here, we assessed ilixadencel as a single agent and combined with sorafenib in advanced HCC. Of 17 HCC patients enrolled, 12 patients received ilixadencel at the dose of 10 x 106 cells (six as monotherapy and six in combination with sorafenib), and five received ilixadencel at the dose of 20 x 106 cells as monotherapy. The primary objective was to evaluate tolerability. All patients had at least one adverse event, with 30% of such events considered as treatment-related, with one single treatment-related grade three event. The most common toxicity was grade 1 and 2 fever and chills. Eleven of 15 evaluable patients (73%) showed increased frequency of tumor-specific CD8(+) T cells in peripheral blood. Overall one patient had a partial response (with ilixadencel as monotherapy), and five had stable disease as overall best response per mRECIST. The median time to progression was 5.5 months, and overall survival ranged from 1.6 to 21.4 months. Our study confirms the safety of ilixadencel as single agent or in combination with sorafenib and indicates tumor-specific immunological responses in advanced HCC.
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