ASCO 2025 | Updated results from the Phase I TRAVERSE study in kidney cancer

There have been several challenges in improving the field in solid tumors with the adoptive cell therapy. I would say tumor antigen heterogeneity, which means like what is really the best tumor antigen that we should target, whether it’s a universal antigen for several tumors or like a unique antigen for one tumor. The other challenge was the suppressive tumor microenvironment in these solid tumors, which is more, you know, complicated or complex tumor microenvironment than we see in malignancies. How can we overcome this suppressive tumor microenvironment? In addition to that, how are we able to make the CAR-T cells infiltrate into the tumor. We call them trafficking of the CAR-T cell into the tumor. And also, as important is how we manage toxicities associated with these CAR-T cell products. I would say many studies, they could not move on to phase two or phase three studies just because of toxicity, not because of lack of efficacy or other factors. To that point, this particular product, for instance, the Allo316, it’s a second generation with additional genetic edits that allows it to prevent cytokine release syndrome (CRS) disease, for instance, and eliminate that toxicity. But one unique feature in Allo316 is its ability to deplete the host T cells, which allows for better engraftment of the product and, in a way, enhanced lymphodepletion, like, you know, the better expansion of the CAR-T cells and persistence, and that would translate into better trafficking into the tumor and better efficacy. And in this particular program, the ALLO-316, we also learned how to manage, as I mentioned earlier, the immune cell-associated hemophagocytic lymphohistiocytosis (HLH), which at once was a very serious complication, but in our hands on the program right now, with our treatment diagnosis and treatment strategies, we were able to capture it early and minimize the fatal toxicity associated with it. The other thing that we’re trying to overcome the suppressive tumor environment with is with those third and fourth generation CAR-T cell products where we can introduce more additional edits to overcome this suppressive tumor microenvironment.

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