Neural stem cells target drug delivery
molecules have shown dramatic efficacy against metastatic cancers
in pre-clinical trials.
This new use of NSCs as targeting mechanisms for anticancer drugs could dramatically increase the outlook for patients diagnosed with metastatic cancers, cancers that have spread throughout the body, who usually have very poor prognoses.
The new technique, described in the launch issue of PLoS ONE, makes use of the tendency of NSCs to migrate to diseased and cancerous regions where anti-cancer drugs can then be activated by genes expressed by stem cells at the site of the cancer. The NSCs have been shown to target to even the sub-microscopic cancerous growths believed to cause relapse.
The tumour-finding neural cell line, HB1.F3.C1., originally derived by immortalisation of human fetal primary stem cells, was engineered to encode a secreted form of rabbit carboxylesterase (rCE), an enzyme capable of activating Pfizer's anticancer prodrug Campto / Camptosar (irinotecan).
Mice bearing cancerous growths spread out through the body were injected systemically, first with the modified NSCs, then three days later by Camptosar daily for five days.
Long-term monitoring (over six months) indicated that the treated animals showed a 100 per cent tumour-free survival rate when compared to the control groups (50 per cent survival).
The migration of the NSCs to macroscopic cancerous growths was studied using fluorescence-labeled NSCs to reveal significant build-up at tumour sites with few, if any, NSCs being observed in normal tissue or organs.
Critically, cancer relapses are believed to originate in microscopic residual growths present in bone marrow or at the primary site and so sensitive polymerase chain reaction (PCR) and real-time PCR (RT-PCR) were used to detect biomarkers for both the tumour cells and NSCs. Data collected from bone marrow samples with tumours that were not microscopically detectable showed that the markers were only found in conjunction with each other, suggesting that the stem cells seek out even out the tiniest cancer deposits.
Ideally, NSCs used as targeting entities for drugs should retain both the ability to differentiate in vivo in a predictable and controlled fashion while also being able to sustain replication to allow propagation and expansion at the target sites. Unfortunately, stem cells can often grow to form cancerous growths themselves.
Notably, the immortalised NSCs used in this study do not replicate in the body and are therefore not cancer forming. However, this non-replication would mean that larger numbers of NSCs would have to be engineered before therapy would be possible.
