RB:
I saw it. Their most advanced product candidate bugs me..... not because of the concept, but the name.... neu-sensamide..... sounds like a high-tech condom from Germany.
I am very enthusiastic about both the targeting of budding endothelium (see integrin work from La Jolla Cancer Research Foundation, now Burnham Institute, or something like that) and the use of bacteria to deliver magic stuff (seeGrillot-Courvalin et al., Nature Biotechnology 16: 862). You also do not want to miss the work of David Bermudes (Vion, also doing prodrug stuff).
Any info you can gather on the investment quality of OXi would be appreciated.
Some day something wild is going to work. What can you say about a company that is targeting new endothelium, generating hypoxic environments, and using bacteria to deliver environment-specific genes? Other than "innovative", that is.
Thanks, good stuff. Landuyt is one serious radiation oncologist.
Rick
Cancer Res 1997 Oct 15;57(20):4537-44
Tumor-targeted Salmonella as a novel anticancer vector.
Pawelek JM, Low KB, Bermudes D
Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
sodi@biomed.med.yale.edu
There has been little investigation of bacteria as gene delivery vectors. Here, we demonstrate that genetically engineered
Salmonella have many of the desirable properties of a delivery vector, including targeting of multiple tumors from a distant
inoculation site, selective replication within tumors, tumor retardation, and the ability to express effector genes, such as the
herpes simplex virus thymidine kinase (HSV TK). When wild-type Salmonella were introduced into melanoma-bearing mice,
the bacteria were found within the tumor at levels exceeding 10(9) per g, although as pathogens, they caused the death of the
mice. However, when attenuated, hyperinvasive auxotrophic mutants were used, the tumor-targeting and amplification
phenomena were retained, whereas their pathogenicity was limited. With such attenuated strains, the tumor:liver ratios ranged
between 250:1 and 9000:1. When these auxotrophs were inoculated i.p. into C57B6 mice bearing B16F10 melanomas, they
suppressed tumor growth and prolonged average survival to as much as twice that of untreated mice. A plasmid containing the
HSV TK gene with a beta-lactamase secretion signal was constructed that, when expressed, resulted in translocation to the
periplasm and phosphorylation of the prodrug ganciclovir. Melanoma-bearing animals inoculated with HSV TK-expressing
Salmonella showed ganciclovir-mediated, dose-dependent suppression of tumor growth and prolonged survival in addition to
that seen with bacteria alone. The results demonstrate that attenuated Salmonella would be useful both for inherent antitumor
activity and delivery of therapeutic proteins to cancer cells in vivo. |
