Continuing the recent theme of new and interesting technologies in cancer therapeutics, today’s blog post looks at neolipid technology and examines how a novel Trojan horse strategy might make existing chemotherapy more efficient and effective.
Tumor cells need to consume large amounts of fat to sustain their rapid growth (angiogenesis). Neolipid technology takes advantage of this by entrapping anti-cancer agents inside liposomes, which are microscopic membrane-like structures created from lipids (fats). The tumour then eats the liposome and absorbs the anti-cancer agent at the same time.
One company that is looking at this liposome technology is NeoPharm, a small biotechnology company based in Illinois, who are developing a NeoLipid drug delivery system. Their lead compound in R&D, cintredekin besudotox, is about to enter phase III trials for glioblastoma multiforme (GBM). While GBM is one of the most common types of malignant brain cancers, it is also one of the most aggressive. It typically spreads and grows tentacle-like within normal brain tissue, often damaging adjacent tissues as it grows uncontrollably. The NCI described the agent thus:
"… composed of interleukin-13 (IL13), a pleiotropic immunoregulatory
cytokine, linked to a mutated form of pseudomonas exotoxin A; this
agent targets and kills tumor cells that express the IL13 receptor
(IL13R). The IL13 moiety attaches to the IL13R on the tumor cell
membrane, facilitating the entry of the exotoxin. The exotoxin moiety
induces caspase-mediated apoptosis of tumor cells via a mechanism
involving mitochondrial damage; it also catalyzes the transfer of ADP
ribose from nicotinamide adenine dinucleotide (NAD) to elongation
factor-2 in eukaryotic cells, thereby inactivating elongation factor 2
and inhibiting protein synthesis."
Over the last 20 years there has been very little improvement in treatment success in GBM and patients often survive only a year or so, despite aggressive surgery, radiation and chemotherapy. The biggest barrier to treatment is targeting the cancer cells without damaging the normal healthy brain cells. GBM is also more resistant to treatment than most cancers because few drugs are able to successfully cross the blood-brain barrier.
How is NeoPharm’s compound cintredekin besudotox different from others that have failed in R&D? Firstly, it is delivered by micro-infusion into the brain rather than via traditional intravenous infusion, which limits its toxicities elsewhere in the body. Secondly, it is hoped that the liposomes will be absorbed by the fat hungry tumour, thereby enabling more chemotherapy to reach the intended target where it is most needed. Thirdly, it targets IL13, which is found on the surface of some cancers. It will be interesting to see if inhibiting IL13 is critical to the survival of the brain tumour.
This combination of regional and molecular targeting is both novel and fascinating; the results for the ongoing phase III trial will determine whether the scientific approach is a valid one or not.