ASCO 2025 | The potential use of multi-virus-specific T-cells to enhance the activity of bispecifics in lymphoma

So, bispecific antibodies have been an exciting development in the field of lymphoma, with very promising response rates in initial clinical trials. 60% overall response rates, with about 40% of patients achieving a complete response. Real-world data, the responses are a little bit more limited, and the median duration of response, even in trials, is only about five months. So, you know, while complete responses are very durable, most patients are not having the benefit of these treatments, or at least not long-term benefit. There are many factors associated with a lack of response, and we’re kind of figuring that out, and there are a lot of different reports with not one consistent message, but several of them are immune-dependent. 

So multivirus-specific T-cells are allogeneic T-cells that we produce by taking whole blood PBMCs and then we activate them to viral peptides and expand them ex vivo. Because they’re expanded towards virus antigens, so we use EBV, CMV, BK virus, and adenovirus, they’re selected towards these viruses and we don’t see graft-versus-host disease in hundreds of treated patients that we’ve treated for viral infections. And these T-cells have immediate effector function. So they have a lot of cytokine secretion and expansion, more so than we would see with regular PBMCs. 

What we looked at was in, you know, basically in test tubes and in vitro experiments, we evaluated their efficacy and their expansion compared to whole blood PBMCs. And we found that there’s about an 86-fold expansion of activated T-cells. So that’s using CD25 as a marker of activation. Compared to regular PBMCs, we have about an eightfold expansion. So significantly more T-cells, more expansion, and then when it comes to cytotoxicity, when we looked at BJAB lymphoma cells, we found that regular, at a one-to-one ratio, PBMCs decreased the number of lymphoma cells by about 33% by day one, but then the tumor cells outgrew the antibody. However, when we use the MVSTs, by day one we had about a 45% decrease, and by day two, 95% of the tumor cells were gone. So we’re seeing at least in these very, very initial preliminary experiments, a lot more cytokine secretion, activation, expansion, and cytotoxicity. So I think very promising, you know, further studies, it’s preliminary data, more research needs to be done, but I think an approach to maybe help us really move these antibodies to help benefit more patients.

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