Life Research Technologies, Wien, Austria
Marianne Imhof , Markus Lipovac , Lukas Angleitner-Boubenizek , Johannes Barta , Ivan Gomez , Astrid Hrdina , Ewa Krupa , Judith Lafleur , Istvan Lang , Katharin Pieta , Heike Rottmann , Martin Imhof
Background: Prognosis of ovarian cancer remains poor after initial responsiveness to surgery and chemotherapy followed by high recurrence and mortality rates and new experimental approaches are warranted. Our goal was to evaluate a novel DC-based vaccine, which exploits a unique dual loading strategy to amplify specific anti-tumor short- and long-term immune responses to delay or even prevent recurrent and metastatic disease. Methods: Monocytes were collected via apheresis, matured into DCs and pulsed with two universal tumor associated antigens (uTAA) in our GMP facility. DCs were loaded with TERT and Survivin via two different pathways (mRNA and peptide) to elicit CD8+ and CD4+T cells directly. Endpoints of the study were tolerability and safety, immunological and clinical responses. T cell responses against the IMP and loaded antigens were evaluated by cytokine bead array (CBA) and intracellular staining assays. Results: 15 non HLA-restricted patients with advanced ovarian cancer were enrolled 8 weeks after standard treatment (surgery and chemotherapy). Each patient was vaccinated intradermally on a weekly or fortnightly basis with a maximum of 8 doses of 13*106 double loaded DCs. The majority of treatment related side effects were grade 1 fever and erythema. Overall the therapy was well tolerated. Immune response data is available for 14/15 patients, 1 was withdrawn after the first administration. The IMP leads to strong immune responses with high frequency (>90%), which is proven for both uTAAs in CD8+ as well as CD4+ T cells. A clear positive trend in progression free survival is demonstrated compared to matched historical control. Conclusions: Therapy with our unique double loaded DC vaccine was feasible, safe and well-tolerated by patients. The vaccine was highly immune stimulatory and elicited both, long-term and short-term anti-tumor immune responses, establishing a promising platform for immune therapy for ovarian cancer and all solid tumors in general. The first two authors contributed equally. Clinical trial information: NCT01456065.
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