DC vaccination using allogeneic tumor lysate pulsing induces mesothelin-specific T cells in malignant mesothelioma patients
P.L. de Goeje1*, Y. Klaver2*, M.E.H. Kaijen-Lambers1, K. Bezemer1, R. Cornelissen1, R.W. Hendriks1, R. Debets2, J.G.J.V. Aerts1
1Department of Pulmonary Medicine and 2Laboratory of Tumor Immunology, Department of Medical Oncology, Erasmus MC, Rotterdam
*Authors contributed equally
Mesothelioma is a malignancy of pleural lining cells with limited treatment options. We have conducted a phase I clinical trial in which 9 mesothelioma patients were vaccinated 4 or 5 times with 10, 25 or 50 million dendritic cells (DCs) that were pulsed with a standardized batch of allogeneic tumor lysate. Here, we set out to characterize treatment-induced changes in numbers and phenotype of various immune cells, with a focus on tumor-specific CD8+ T cells.
Numbers of peripheral CD4 T, CD8 T and B cells were increased, as well as the % CD4 T cells expressing ICOS, suggestive for DC-induced activation of adaptive immune cells. Skin test responses against lysate-loaded DCs were positive in all patients, further supporting immune cell activation and occurrence of T cell memory. Next, T cells were isolated from positive skin tests and used to assess specificity towards mesothelin, which proved to be present in the tumor lysate and showed expression in all patient tumors. In 4/7 evaluable HLA-A2+ patients, CD8 T cells reactive against two mesothelin epitopes as measured by peptide-MHC multimer staining. Frequencies (~0.1% of CD8 T cells) of mesothelin-specific T cells were in the expected range, based on known literature.
In conclusion, we demonstrated that treatment with DCs pulsed with a universal batch of allogeneic tumor lysate is able to evoke a tumor-specific T cell response, exemplified by the selection of mesothelin-specific T cells. We are currently looking into T cell responsiveness against a broader set of antigens, including epitopes outside HLA-A2, to enable future patient stratification for treatment with allogeneic lysate-pulsed DCs.
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