ASCO 2025 | What does the future hold for T-cell engagers in oncology?
With the advent of therapies targeting PD-(L)1 such pembrolizumab and nivolumab, there has been a push for more immunotherapies. Alexander Spira, MD, PhD, FACP, FASCO, NEXT Oncology Virginia, Fairfax, VA, highlights the potential of T-cell engagers, noting that despite initial disappointment with other immunotherapies and adverse events such as like cytokine release syndrome, this class of drugs holds promise with clear evidence of activity and potential for innovation, particularly in solid tumors. This interview took place during the 2025 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
Immunotherapy, there was a lot of big push after the advent of nivolumab, pembrolizumab, all the PD-1, PD-L1 drugs, and the CTLA-4 drugs, with a lot of drugs coming out. And there was a little bit of a disappointment because there were a lot of studies being done, and they kind of went to the back burner because most of them were negative. Recently, the TIGIT story has been up and down, mostly down...
Immunotherapy, there was a lot of big push after the advent of nivolumab, pembrolizumab, all the PD-1, PD-L1 drugs, and the CTLA-4 drugs, with a lot of drugs coming out. And there was a little bit of a disappointment because there were a lot of studies being done, and they kind of went to the back burner because most of them were negative. Recently, the TIGIT story has been up and down, mostly down. Really excited about the T-cell engagers. The challenge, you know, they’re a different kind of endgame therapy. The way they work is by binding a tumor antigen, but also having usually a CD3, but can be others, motif that brings in T-cells along with it. There’s clear evidence of activity for some. The approval of talimogene laherparepvec in small cell lung cancer really opened up the doors for solid tumors. So I think there’s going to be a lot of innovation for that, especially as you have a lot of antigens you can target and kind of rearrange the deck chairs with the antibodies, so to speak, with different targets, but also keeping that CD3 on there. So to me, that’s the way to go. The challenge is that the studies have a lot of potential side effects like cytokine release syndrome, so they’re a challenge to do, but I think there’s going to be a lot of effort in the next couple of years given what we’ve seen so far. Great. Thank you.
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