Savio L-Y Woo, PHD, DSC; Mount Sinai School of Medicine; Clinical Translational Research Award:

My history with the Breast Cancer Research Program goes back a number of years. We started out with an award to conduct immune based gene therapy approach for metastatic breast cancer and that was back in the late nineties. We learned from that award we show that by the use of a common cold virus that has been disarmed instead we use a gene that has been put into the virus if we inject them into the breast cancer cells, in mice, and we show that there has been an immune response that has been stimulated that would then come along and reject the cancer cells. And so that was very, very exciting and that was way back then. But then we find that the effect was not long lasting.

So, we looked at another molecule, called a co-stimulation molecule. And the two together we learned that, in a mouse, we have generated not only a transient immune response but a long lasting one as well. But still the effect was not ideal, it was good but not ideal. Because we have stimulated the immune cells to reject the cancer, the cancer learned that in order to survive they have to turn off these immune attacks. This business of turning on and turning off of the immune system is a very intricate control mechanism that are already in our bodies, in our genes, and we use them all the time. So when something goes up, when the target is gone - something goes down, so that we're normal again. So in this case the tumor cells find out, they learn how the body actually naturally turns off the immune system. And so they corrupt this method of turning off the immune attack against the cancer cells so that they can continue to grow and divide. So now we are at a stage and say, if that's the case can we turn off the cells that down-regulate the immune cells for a while. So they'll let the immune system have a better chance to attack the cancer. And we did that, and that's the essence of this study right here.

If we just stick to mice, we just treat them with some placebo control, all the mice die in about forty days. Very shocking, you can see all the mice die. If we inject only this protein that down-regulates the immune cells, it doesn't do very much because at this point the immune system is not up-regulated yet. So, you shut down something that's not yet been activated, you don't do much. And look at what happens here, this is a survival curve. These are the number of days that the animals are still surviving, the percentage of the animals that are still living. You can see that in this curve is the animals that were injected with the virus that contains a couple of cytokines and the stimulating protein. OK, that's this treatment alone and we're already seeing a very nice effect relative to this. Right? This is, median survival has been increased by about 20-30 days. And that's very significant. You can think about if a patient has three years and you can increase it by two years, that's very significant. Nothing to laugh at. And we have about 20 percent of the animal actually surviving long term. OK, that's very exciting already. But, when you look at this triple treatment, all of a sudden we see that we have 60 percent of the animals surviving long term and we don't have a median survival because we don't have 50 percent death yet. So, it's an enormously exciting result and that is because we were able to keep the immune system going for a much longer time and a much more robust response against the tumor.

In order to translate this results in mice into patients, what we have been doing is trying to do translational trials in breast cancer patients. So, hopefully by the time we finish the Phase 1 trials of these two molecules, we will be able to add a third molecule and hopefully we can generate some results in patients that are similar to mice. And that would be a fantastic advance in terms of breast cancer treatment.