Intratumoral vaccination with activated allogeneic dendritic cells in patients with newly diganosed metastatic renal cell carcinoma (mRCC).

Authors

null

Anders Magnusson

Department of Radiology, Uppsala University, Uppsala, Sweden

Anders Magnusson , Anna Laurell , Maria Lonnemark , Einar Brekkan , Lars Adamson , Anna Tolf , Bengt Andersson , AnnaCarin Wallgren , Rolf Kiessling , Alex Karlsson-Parra

Organizations

Department of Radiology, Uppsala University, Uppsala, Sweden, Department of Oncology, Uppsala University, Uppsala, Sweden, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden, Department of Oncology-Pathology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden, Department of Pathology, Uppsala University, Uppsala, Sweden, Department of Immunology, Gothenburg, Sweden, Department of Pathology, Uppsala University, Uppsala, Sweden, Department of Immunology, Uppsala University, Uppsala, Sweden

Research Funding

Pharmaceutical/Biotech Company

Background: Accumulating data indicate that the efficient induction of antigen-specific CTLs characterizing viral infections is caused by cross-priming where infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected ”bystander” DCs. Accordingly, we have developed a cellular adjuvant consisting of activated DCs producing high levels of DC-recruiting and DC-maturating factors in a sustained fashion. 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” anti-tumor vaccine when injected intratumorally. Methods: 12 patients with newly diagnosed mRCC (5 with poor prognosis according to Heng criteria) where included in a clinical phase I/II study. Vaccine cells (50 doses) were produced from a leukapheresis-product from one healthy blood donor and subsequently deep-frozen. 5-20 x 10(6) vaccine cells were injected intratumorally twice with 2 weeks interval before nephrectomy. Results: No vaccine-related severe adverse events were observed. 9 out of 11 evaluated patients exhibited an increase in circulating tumor-specific lymphocytes (IFN-gamma ELISPOT) after vaccination. A strong infiltration of CD8+ T cells was found in 7 out of 12 removed kidney tumors, of which 5 tumors, to the best of our knowledge, exhibit the most intensive and general infiltration of CD8+ T cells ever reported in any human solid tumor. Median overall survival (mOS) in the poor prognosis (PP) group is still not reached but has already passed (without addition of targeted therapy) the expected mOS in poor prognosis patients on targeted therapy (9.8 vs 7.8 months). 40% of the patients in the PP-group have to date (Jan 2014) survived for more than 17 months (without addition of targeted therapy) compared to an expected 17 months-survival of 20% in PP patient groups on targeted therapy. Conclusions: Our findings indicate that intratumoral injections of pre-activated allogeneic DCs is safe and induce a systemic CTL-mediated anti-tumor response that may prolong survival in mRCC patients. Clinical trial information: NCT01525017.

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Abstract Details

Meeting

2014 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Developmental Therapeutics - Immunotherapy

Track

Developmental Therapeutics

Sub Track

Vaccines

Clinical Trial Registration Number

NCT01525017

Citation

J Clin Oncol 32:5s, 2014 (suppl; abstr 3085)

DOI

10.1200/jco.2014.32.15_suppl.3085

Abstract #

3085

Poster Bd #

152

Abstract Disclosures