That is a great catch, you may be right. My belief in vaccine therapy for cancer started when I was a fellow. The work being done with whole cell vaccines on melanoma made me a believer in the potential of the vaccine approach. I have seen the potency and effects of the main modes of immunotherapy throughout my career(e.g. antibody, adaptive T cell, BCG, cytokines, & vaccines). BCG is fairly weak and of limited use on it's own. Cytokine treatments can make you so sick they can require hospitalization during treatment with very limited overall survival effect. Adaptive T cell treatment at this point has a questionable role in solid tumors. Antibody treatment such as PD-1 and CTLA-4 are effective to a degree on their own but are quite toxic. I can tell you first hand more toxic in person to most than is discussed in the literature. Response rates as single agents are fairly low, abour 20%,. Also realize, that of those 20% that respond, half of those patients only get a few extra months and half of those patients are miserable(gives you an idea how much room for improvement there is). Combining of antibodies is even more toxic, quite miserable to see in person actually. Yes, you get a nice response rate, I think aroud 50%, but up to half of those can't complete/continue treatment. Also a lot who are able stay on treatment feel like crap on a good day. The "crude" vaccines I saw for melanoma had almost no side effect. Those that responded had disappearance of multiple "bulky" tumors and sustained responses in many cases. Unfortunately, response rates were just too low for the early vaccines. I am fully cofident as more is learned the vaccine approach will be the future of treatment. If not on it's own, atleast part of a "cocktail". Time has taught us that mesenchymal tumors are the most immunogenic. Such cancers with the epithelial-mesenchymal transition include melanoma, non small cell of the lung, colorectal, GBM and prostate. There is every reason to believe that these cancers can be treated with "L" and the hope of an improvent of PFS and OS. The data that we are aware of for mesenchymal glioblastoma helps support this hypothesis. Some of the cancers I have listed, even when removed in surgery for "cure", have very high recurrence rates. Antibody treatment such as PD-1 have or will most likely have an effect on the cancers I mentioned, but in the overall picture it is limited. DCVax has the potential increase those effects, making it attractive to those drug makers. In the case of tumors that are clinically removed, "L" could handle the low volume residual disease that causes the recurrence in those patients. This knowing that the potency of "L" would most likely require lower volume disease to be successful.
Anyways, starting ramble on. It is just hard for me to get in all my thoughts in a short post. I know I am a horrible writer. Just saying I agree with your thoughts and some of the reasons. My hope is that "L" gets some type of approval for mesenchymal GBM in the very near future and the trials for "L" in some of these other cancers(or sarcoma) start soon. Hoping for arms using "L" alone and in combination with different types of antibody treatment.. Hope that is a reasonable wish?
