ESMO 2026 | Humoral immunity to melanocytic antigens and checkpoint blockade benefit

Basically, what this abstract showed is I’ll divide it into two parts. First, they looked at the relevance or the role of B cells and their specific antibodies, right, that our body produces, again, whatever we have in this case against melanoma. So it’s going to be against the MDAs, right? The melanocytic differentiated antigens, in this case, were GP100 and TRP2, right? So first, they looked at that, more kind of a biomarker. And what they have seen is that if we compare baseline with on-treatment, they saw an increment, a significant increment of the titers of those antibodies, both, okay? And they did not see that in the non-responders. So that’s already a signal. What is not clear to me is if that is a passive or a passenger effect or it’s a driver effect. So I don’t know if that increment is part of the immune response against the tumor or it’s just like a consequence of cell death. But anyway, that’s something. But then they took everything to a different level. They want to use that as a treatment option, which I found very interesting. Of course, very preliminary data, but they have three pieces of information that are very important. One, they show that these antigens that are normally intracellular, in fact, they could be seen in the membrane, which is very important to be able to target. So that’s the first thing. The second thing, they did two in vitro assays, the ADCC and the ADCP assay, and both showed that some of these antibodies from some of the patients, they were in fact functional to kill tumor cells. And the third is that very preliminary, they didn’t show much data, but it’s in vivo. So they have an in vivo model where they saw, in fact, an anti-tumor effect with those antibodies alone. And when we add NK cells, even more. So, of course, very preliminary. My questions about this study, mainly two. One is, are we sure that those antigens are a good target? And they might be. But I’m asking, are they specific enough? So the majority of melanoma cells they express. They should express because it’s part of the development and differentiation. But the other thing is probably other normal cells also express and then could lead to some toxicities. That’s the first question. My second question is, are we sure monoclonal antibodies are the best way to target those antigens? Again, could be, but that’s a question for the field, because when we looked at what studies are being done out there, we have many strategies, bispecifics, vaccine, mRNA, so then what’s the best way, right? So could be that, could be something else, but that’s for the field to decide, yeah.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.