Hybrid cell, useful as therapeutic vaccine against cancer and viral, bacterial and protozoal infections, comprises allogeneic dendritic cells fused to autologous non-dendritic cells

摘要

A hybrid cell (I) comprising a mature dendritic cell (DC) fused to a non-dendritic cell which is freshly isolated or obtained from a primary cell culture and where DC and non-DC are allogeneic to each other, is new. Independent claims are also included for the following: (1) making (M1) (I) comprising subjecting a population of mature DCs and non-DCs allogeneic to the DCs to conditions that promote cell fusion; (2) a kit comprising a sample containing a population of mature DCs in one or more containers and instructions for its use in treating or preventing cancer or an infectious disease or in making (I); (3) treating or preventing (M2) cancer or an infectious disease in a mammal comprising administering a therapeutically active amount of (I) which shares at least one class I major histocompatibility complex (MHC) allele with the mammal; and (4) preventing a cancer in an individual having a predisposition for the cancer comprising M2 where the non-dendritic cell displays the antigenicity of an antigen associated with the cancer. - ACTIVITY : Cytostatic; Antibacterial; Virucide; Protozoacide; Antiparasitic. The effect of the hybrid cells as vaccines for treating cancer was studied in 17 patients with renal cell carcinoma. The hybrid cells were formed by electrofusion of 5 X 10 to the power of 7> autologous cells derived from renal cell carcinoma tissue with 5 X 10 to the power of 7> allogeneic dendritic cells. After electrofusion and irradiation with 200 Gy, the vaccine was immediately injected. Freshly-prepared booster vaccinations were administered after 6 weeks, followed by a re-evaluation of the patients 6 weeks later. After 13 months, 4 patients completely rejected all metastatic tumor lesions, one presented a mixed response, and 2 had a tumor mass reduction of greater than 50%. This demonstrated induction of human leukocyte antigen (HLA)-A2-restricted cytotoxic T cells reactive with the MucI tumor-associated antigen and recruitment of CD8+ lymphocytes into tumor challenge sites. The hybrid cell vaccination was well tolerated by all patients and there were no serious adverse effects. These results indicated that hybrid cell vaccination was a safe and effective therapy for renal cell carcinoma. - MECHANISM OF ACTION : Vaccine.