Joshua Brody, MD, discusses the gratification of the crossover between medicine and science at the 34th Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019).
Here at SITC 2019, a lot of exciting oral presentations, some very exciting poster presentations that we saw as well. I think in big concept what is most exciting is the remarkable bringing together of scientists and clinicians here. It is very gratifying that, in the old days science was in 1 place and medicine was in another place. You could memorize the Krebs cycle, but it didn’t actually affect our patient care from day-to-day, and it is completely not the case now. We are seeing early-phase discoveries that can become biomarkers in clinical trials immediately.
Some work that we presented from one of the brilliant students in my lab, was looking at the importance of Fas insensitivity to all types of T-cell therapies, whether it be (chimeric antigen receptor; CAR) T-cells or bi-specific antibody therapy. We already are starting to look at Fas in the tumor specimens of our patients treated with those therapies. We even got to look in the aggregate data from a large CAR T-cell trial, and we saw that Fas-predicted long-term regressions overall survival more so than other biomarkers that we thought would be good predictions, like CD19, that targets that therapy. So, things go form basic science translation to biomarkers and potential therapies for our patients. So, overall the cross-section of science and medicine at SITC is remarkable.
I saw a lot of great things this year at SITC. I have to acknowledge in this entire group of presentations that we call the intratumoral immunotherapies cohort, we saw that there a lot of novel approaches. Some of the furthest along (was the review of) TLR9 agonism for melanoma, especially for patients who were anti-checkpoint blockade refractory to anti-PD1 blockade or CTLA4 blockade, still having great responses with the combination of intratumoral TLR9 agonist checkpoint blockade.
For the past few years, a lot of the focus had been on what is the next PD1 or CTLA4 therapy. But they were really focused on the next thing on the T-cell, whereas, some of these intratumoral therapies recognize the importance of intratumoral immunomodulation in the myeloid compartment, and especially on intratumoral dendritic cells and their ability to cross-present antigens. So, with the TLR9 agonist, patients were an example of that. (There were also) a number of great examples of intratumoral immunomodulation, and other big picture examples of modifying tumor microenvironment towards this effect. So, I think that has been one of the most exciting themes that I saw this year at SITC.
We have our foot in the door for intratumoral immunomodulation, and that is with the FDA-approved oncolytic virus we call T-VEC, but so far its application is a bit narrow. We have ongoing trials of T-VEC with checkpoint blockade for advanced melanoma, but also other advanced stage tumors, and those are very promising. If they don’t hit the mark, but we can still learn great lessons from them, I think that they will bring acknowledgement to local therapy-inducing systemic anti-tumor responses. It seems to me a no-brainer than in 5 years from now we will have some ways of using intratumoral immunomodulation. And these should be FDA approved within 5 years to improve the efficacy of checkpoint blockade, at the very least for melanoma, but for other tumor types as well.
If anything, one of the big differences was that momentum of checkpoint blockade has been a miraculous breakthrough. If it weren’t for checkpoint blockade, the whole field of immunotherapy would be barely on the map. It drove people to focus on systemic immunotherapy. Now that we’ve seen some moderate results from those, it has opened up the field a little bit more to not just focus on the T-cell, but for myeloid cells that primer other cells. That does seem like a difference from SITC 2018 to SITC 2019.