Immunoprotection against murine bladder carcinoma by octaarginine-modified liposomes incorporating cell wall of Mycobacterium bovis bacillus Calmette-Guérin
Article first published online: 25 NOV 2008
© 2008 THE AUTHORS. JOURNAL COMPILATION © 2008 BJU INTERNATIONAL
Volume 103, Issue 5, pages 686–693, March 2009
How to Cite
Joraku, A., Homhuan, A., Kawai, K., Yamamoto, T., Miyazaki, J., Kogure, K., Yano, I., Harashima, H. and Akaza, H. (2009), Immunoprotection against murine bladder carcinoma by octaarginine-modified liposomes incorporating cell wall of Mycobacterium bovis bacillus Calmette-Guérin. BJU International, 103: 686–693. doi: 10.1111/j.1464-410X.2008.08235.x
- Issue published online: 16 FEB 2009
- Article first published online: 25 NOV 2008
- Accepted for publication 8 August 2008
- mycobacterial cell wall;
- octaarginine-modified liposomes;
- bladder neoplasm;
- drug delivery system
To develop a prototype of a non-live bacterial agent that consists of a cell wall (CW) preparation from heat-killed bacillus Calmette-Guérin (BCG-CW) incorporated into octaarginine-modified cationized liposomes as a vector (R8-liposome-BCG-CW), and to evaluate its immunoprotective potentiation in mice, as although BCG is an established effective immunotherapy for nonmuscle-invasive bladder cancer, more active and less toxic treatments are needed.
MATERIALS AND METHODS
The cellular interaction of R8-liposome-BCG-CW co-cultured with mouse bladder cancer cell line (MBT-2) was examined by confocal laser scanning microscopy. MBT-2 cells (7 × 105) were subcutaneously inoculated with 1 mg BCG, 0.1 mg or 1 mg BCG-CW, 0.1 mg or 1 mg R8-liposome-BCG-CW in female C3H/HeN mice. The MBT-2 cells pretreated with BCG or R8-liposome-BCG-CW were re-challenged at 6 weeks. The sizes of the primary and re-challenged tumours were evaluated at 4 and 10 weeks, respectively.
Confocal laser scanning microscopy showed the enhanced incorporation of R8-liposome-BCG-CW into MBT-2 cells after 1 h of co-incubation. 0.1 mg R8-liposome-BCG-CW completely inhibited the growth of MBT-2 tumours while 0.1 mg BCG-CW alone did not (P = 0.002). Mice vaccinated with a mixture of MBT-2 cells and R8-liposome-BCG-CW inhibited the growth of re-challenged tumour of MBT-2 cells pretreated with BCG or R8-liposome-BCG-CW but did not inhibit that of MBT-2 cells with no pretreatment at 10 weeks, with mean (sd) tumours sizes of 54 (60) mm2 (P < 0.001) or 69 (43) mm2 (P = 0.003) compared with 309 (125) mm2, respectively.
The immunotherapeutic potential of BCG-CW was enhanced by improving cellular association using the R8-liposomes delivery system. Development of this non-live bacterial agent may contribute to providing a more active and less toxic tool as a substitute for live BCG as immunotherapy against nonmuscle-invasive bladder cancer in the future.