ESMO Immuno-Oncology 2025 | Intratumoral immunotherapies to activate non-T-cell inflamed tumors

Yeah, thank you very much. And thank you for inviting me to speak with you. Yeah, I’m going to talk about how I’m transforming the non-T-cell inflamed tumor microenvironment. And the way we are doing it in our center is mainly by immunomodulatory vaccines. And the difference between immunomodulatory vaccines and traditional cancer vaccines is that we’re not targeting the neoepitopes of the cancer cells, but we are targeting microenvironment antigens, which are expressed not only by cancer cells, but also by other cells of the microenvironment, like immune-regulatory cells or even fibroblasts and cells like that. So basically, this year’s ESMO, which was one or two months ago, there was very, very interesting phase three data presented by Hessen and co-workers who showed very, very interesting data with an immune-modulatory vaccine targeting IDO and PD-L1. And they showed, I think it was, the median overall survival of the median progression, sorry, the median progression-free survival was 17 months versus 11 months in the control group. And it was, even in the PD-L1 positive patients, it was 25 months versus 11 months. And you can say, especially interesting for my talk was that in the PD-1 naive patients, it was 25 months versus 11 months. And you can say especially interesting for my talk was that in the PD-1 negative patients, which are the ones that have non-T-cell inflamed microenvironments, the response rates were the median progression-free survival in the vaccination plus PD-1 was 17 months versus only three months in the control arm. So that was PD-1 monotherapy. So this really highlights that the immune-modulatory vaccines do something to these patients that have, unfortunately, these non-T-cell inflamed environments. The phase three data was based on a phase two trial, which was conducted in my center at the Copenhagen University Hospital at Herlev. And what I’m presenting at ESMO is based on material from this trial, where we have been able to activate and isolate vaccine-specific T-cells. We have melanoma cells cultured from the patients. We have immune cells isolated. So we have been able to, in vitro, to basically study what happens in the patients in the tumor microenvironment during therapy. And what I will show data on is basically that we know that the vaccine is inducing both CD8 and CD4 T cell responses, and we know that the CD8 cells can kill target cells, but we also have a lot of CD4 cells. And I show in the talk that these CD4 vaccine-induced T cells are able to target directly both cancer cells, but especially myeloid cells, which they can convert from being immunoregulatory, immunosuppressive, to actually anti-tumor cells that support the T-cell inflammation and the response. So basically, we have data showing the direct targeting of the myeloid cells, but we also show that indirectly by the activation of these T cells in the microenvironment, we convert the microenvironment from a suppressive to an inflamed environment. Then I will, in the end, also talk about some other interesting targets which are being developed, like arginase and TGF-beta vaccines, where we can show that we can target fibrosis. And that is, of course, not so clinically developed, but it will be, hopefully, in the coming years, very interesting for our vaccines. I think that will be all my talk.

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