Therapeutic dendritic cell vaccine preparation using tumor RNA transfection: A promising approach for the treatment of prostate cancer

Juliana M Sousa-Canavez¹ , Flavio C Canavez¹ , Kátia RM Leite¹^,2 and Luiz H Camara-Lopes¹

¹Oncocell Division, Genoa Biotechnology SA, Alameda Ministro Rocha Azevedo, 346, 1^stfloor, 01410-000, São Paulo, SP, Brazil

²Laboratório de Investigação Médica da Disciplina de Urologia da Faculdade de Medicina de USP-LIM 55, São Paulo, SP, Brazil

author email corresponding author email

Genetic Vaccines and Therapy 2008, 6:2doi:10.1186/1479-0556-6-2


Published:	18 January 2008

Abstract

Background

Early prostate adenocarcinoma can be diagnosed through seric prostate-specific antigen (PSA) screenings. However, a fraction of patients progress to an incurable metastatic disease. Therefore, novel therapies for treating these patients are extremely desirable. Therapeutic vaccines based on Dendritic Cells (DCs) carrying tumor antigens have emerged as a promising strategy to initiate an immune response against tumor cells. These vaccines can be prepared using different methodologies, such as the application of tumor mRNA described in this work.

Methods

Mature and immature DCs were obtained in vitro by adding specific cytokines to monocyte cell cultures. RNA extracted from prostate tumor lineage (LNCAP) was introduced into these cells by electroporation and co-incubation. Transfection success was measured by immunocytochemistry of the PSA expression level in DCs.

Results

Cell surface markers, including CD14, CD80, CD86, CCR7, CD11c, and CD1a, confirmed mature and immature DC phenotypes. Both cell maturation stages were successfully used for RNA introduction as shown by PSA characterization.

Conclusion

Our data support the use of mature and immature DCs for vaccine preparation with either RNA electroporation or RNA co-incubation. The highest efficiency, however, was observed when RNA was delivered by electroporation into mature DCs. Due to in vitro RNA transcription, this method allows small tumors to be used for DC vaccine preparation; it is therefore a promising approach for the treatment of metastatic prostate cancer.