Abstract Malignant Mesothelioma (MM) is an aggressive disease without curative treatment options. Treatment with chemotherapy and surgery is accompanied with high incidences of local recurrences. Novel therapeutic treatment options are urgently needed and immunotherapy may be a new player in the field of MM. We have previously shown the feasibility of dendritic cell (DC) immunotherapy in MM (Hegmans, et al. Am J Respir Crit Care Med 2010). In these studies DC were loaded with autologous tumor cell lysate. Apart from safety also radiographical responses were found and survival was promising. However autologous tumor cell lysate has major drawbacks both in availability, quality and logistics. Therefore a new concept was developed, based on DC loading with a tumor cell lysate derived from human MM cell lines. In a murine MM model allogenic loading of DC's was equally safe, and effective as autologous (data submitted). We have developed a clinical grade allogenic batch of tumorcell lysate which is now used in a phase I study where patient diagnosed with MM are treated. This batch has been generated according to GMP and GLP regulations and a patent is pending. Orphan drug designation has been obtained from both FDA and EMA. For the trial, major inclusion criteria are chemonaïve patients or patients with a disease controle according to modified RECIST after standard chemotherapy. Patients with a need for high dosages of immunosuppressive therapy are excluded. In the study patients undergo a leukapheresis to collect monocytes. These monocytes are in vitro differentiated to DC's and pulsed with tumor lysate according to the previously described protocol. DCs are re-injected intravenous and intradermally every 2 weeks to determine toxicity. A 3*3 design study is initiated where chosen dosages are 10, 25 and 50* million cells. Primary endpoint is safety. Secondary endpoints are radiological responses according to modified RECIST for mesothelioma, progression free survival and overall survival. At present the study is open for inclusion. At the meeting results of the first dose cohorts will be presented. This will be the first in human study in MM with allogenic tumor cell loaded DC. In case no safety issues are encountered this may open the field of combination treatments (e.g. immunecheckpoint inhibition combined with DC treatment) to increase the population of patients who benefit from immunotherapeutic treatment options. Citation Format: Joachim G. Aerts, Robin Cornelissen, Cor van der Leest, Ferry Eskens, Koen bezemer, Margaretha Kaijen, Rudi Hendriks, Joost Hegmans, Henk C. Hoogsteden. Autologous dendritic cells loaded with allogeneic tumor cell lysate in patients with mesothelioma: A phase I study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT229. doi:10.1158/1538-7445.AM2015-CT229