Dendritic-tumor hybrid cell therapeutic vaccination for metastatic melanoma and renal cell carcinoma patients

JAM Barbuto, MD, PhDab, LF Ensina MD a, AR Neves BSc a, PC Bergami-Santos PhD ab, R Marques MD b, KRM Leite MD, PhD b, LH Camara-Lopes MD b, AC Buzaid MD b

aInstituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, SP Brazil bHospital Sirio-Libanes, Sao Paulo, SP, Brazil

AIM: We describe preliminary data of a protocol, started in March, 2001, that uses dendritic cells (DC)-tumor cell hybrids for the therapeutic vaccination of metastatic cancer patients. METHODS: Patients with metastatic melanoma (n=7) and renal cell carcinoma (n=9) were included. Tumor was obtained and single tumor cell suspensions were prepared, frozen and kept in liquid nitrogen. DC were generated by culturing adherent mononuclear cells from allogeneic healthy donors with GM-CSF and IL-4. DC were activated with TNF-alpha and electrofused with thawed tumor cells. The fusion product was then injected in the patients. Hybrid cell vaccines were produced and injected every six weeks until progression of disease. RESULTS: Until now, one patient received six doses of the vaccine, two received five, one received four, four received three, two received two and six received one dose. Eight patients are still under treatment (at the 6th, 3rd or 1st dose). No side effects were noted. DTH reactions to four recall antigens, which were negative before vaccination in six of the nine patients evaluated became positive in eight, thereafter. Likewise, lymphocyte proliferative responses to PHA and to tumor cells increased after vaccine treatment. CONCLUSIONS: These preliminary data indicate that hybrid dendritic-tumor cell vaccine are safe and seem to allow immune function restoration of patients. Its clinical efficacy cannot be evaluated yet.

KEY WORDS: dendritic cells.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Metastasis.