Evidence of Efficacy
In Vitro Study
Overcoming Multidrug Resistance In Human Ovarian Cell Line
A study on chemo-resistant ovarian carcinoma cell line SKVLB demonstrated that is takes 10 times more dox to kill 50% of the cells in the resistant cell line than with AFP-Dox which seems to be able to overcome the resistance by binding to receptors found on the resistant cells and transporting dox directly into the cell bypassing the cell membrance pumps.Moskaleva et al. (1997), Cell Biol. Internat., 21, 793-799
In Vivo Tumor Volume
In this study 3 groups of mice were treated with either saline or with equal doses of paclitaxel (Taxol®) delivered either as a conventional paclitaxel formulation (red line) or carried by AFP (ACT-901) (blue line). The graph illustrates that tumor growth is significantly reduced when paclitaxel is delivered by AFP (ACT-901) compared to the same dose of free paclitaxel.UHN, Princess Margaret Cancer Centre
In Vivo Survival Study
In this study several groups of mice were treated with various doses of paclitaxel (Taxol®) or ACT-901 (AFP + paclitaxel). The black line shows the control group that was given only saline. All mice were dead by day 24.
The 2 red lines show survival of mice given low (dotted red line) or high (solid red line) of paclitaxel. Low dose paclitaxel had no effect and did not improve survival rates.
The same low paclitaxel dose (blue line) delivered as ACT-901 (AFP + paclitaxel) significantly improved survival and was even better than a high dose paclitaxel.
There were 7 mice per group in this study. Low dose paclitaxel and ACT-901 (AFP + paclitaxel) were given every other day for 3 weeks at the same dose of paclitaxel, while in high dose paclitaxel group treatment was daily for 3 weeks.
Mice in the high paclitaxel group (solid red line) showed signs of severe toxicity, with weight loss and lack of normal grooming behaviour and excessive irritability. The ACT-901 (AFP + paclitaxel) group exhibited no signs of toxicity.
There was also significant vein sclerorsing in the high paclitaxel group but not in the ACT-901 (AFP + paclitaxel) group.UHN, Princess Margaret Cancer Centre
In Vivo Xenograft Study
In this study 2 groups of mice were treated with saline (control group) or ACT-902. Dotted lines show individual tumor volumes in control mice. All mice were dead by day 24.
Solid lines show changes in tumor volumes of mice treated with ACT-902. 5 out of 6 ACT-902 treated tumors show complete regression of tumors by day 7 of treatment with no further growth thereafter. One tumor was unresponsive and continued to grow.
It should be noted that POP-92 cancer cells are from patient with BRAF mutated colorectal cancer. This type of cancer is highly resistant to chemotherapy resulting in poor prognosis for patients with this cancer type.UHN, Princess Margaret Cancer Centre
In Vivo MDSCs Study | PDX Model
ACT-902 causes significant reduction in Myeloid Derived Suppressor Cells (MDSCs) that play a major role in protecting cancer cells from host immune system. Thus AFP conjugates are likely to have both, direct cytotoxic effect on cancer cells and immune check point inhibition effect without toxicity.UHN, Princess Margaret Cancer Centre