RNA-DC vaccination in multiple myeloma.

Patients with multiple myeloma (MM) are treated with intensive chemotherapy, which frequently induces a status of minimal residual disease, but finally all patients will relapse. Allogeneic transplantation as a form of immunotherapy may prolong remission and even cures the disease, but only in a minority of the patients and with significant toxicity. In a pilot study we vaccinated MM patients with mature DC loaded with idiotype as an alternative form of immunotherapy. We showed the feasibility and a very limited toxicity, but the idiotype antigen appeared only weakly immunogenic. In this study we will vaccinate with 3 different proteins, Mage-3, Survivin and BCMA, all shown to be highly expressed on malignant plasma cells. Autologous mature DC, electroporated with tumor associated antigen messenger RNA, will be used to present the antigens to the immune system.

The primary goal is to show the capability of monocyte-derived DC after RNA electroporation for multiple antigens to induce an immune response. The secondary objective is to show clinical response.

Patients will be treated by 4 DC vaccinations at 2 weeks interval. In case of response the procedure can be repeated to boost the immune response.

For follow-up we will collect blood (at day 14, 28, 42, 56 and 70 after DC vaccination) and bone marrow aspirates (at 3, 6, 12 months after chemotherapy during 1st year).

Patients monocytes will collected by apheresis. Patients will be vaccinated intravenous and intradermal at 4 occasions with 2 weeks interval. Monitoring will be done for toxicity, immune response and minimal residual disease.