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The challenge of targeting solid tumors with T cells, TIL therapies, TCR Ts | Neil Sheppard | Stem Cell Jungle

While solid tumors represent the vast majority of cancers, most commercial cell therapies target hematological malignancies. Why ? What are the most promising T cell-based strategies in solid tumors ? A discussion with Neil Sheppard, D.Phil, Adjunct Associate Professor in the Department of Pathology & Laboratory Medicine, and Head of the T Cell Engineering Lab (TCEL), at the Center for Cellular Immunotherapies (CCI) at the University of Pennsylvania has a 20-year experience in the field of immunotherapies and vaccines.

Transcript:

 

And specifically what do you think about what makes the solid tumor a very specific case namely the tumor micro-environment or TME. And where does the field go relative to that ?

Great question. So yes, you know solid tumors represent 90 percent of cancer. So clearly, there’s much more medical need in solid tumors than in hematological malignancies.

But solid tumors are a much harder setting. So we do have you know some bright points on the horizon. TIL therapy has repeatedly shown that you can get about 50% objective response rate in patients with melanoma. There are also now reports of responses in ovarian cancer was reported from the very beginning but we’ve had some sporadic updates on that – there was a wonderful breast cancer patient, that was studied a few years ago by the NIH. They managed to get from stage four into remission using TIL-based therapy. And companies like lovance they are actually working towards commercializing TILs for the first time. So again, in the next couple of years we hope to see a commercialized TIL, probably melanoma first, but they have also shown responses in cervical cancer and also in lung cancer. Which is a really big deal, big indication. So that shows you that T cells can achieve responses in solid tumors, which is exciting. And builds on our knowledge of what checkpoint agents do. There are also the TCR-T companies. People like Adaptimmune, Immatics. They have also shown that they can get responses in sarcoma. And I think there’s a few patients that responded in esophageal gastric junction cancer, ovarian cancer, etc.

And so T cell approaches can work. But as of now, we haven’t really seen any reproducible responses in solid tumors with CAR-T cells. There’s been like a sporadic reporting but it they’re always from small uncontrolled trials. Sometimes it was in combination with checkpoints. It’s kind of very murky, very difficult to see what the CAR-T did versus the other agents etc. So there remains this really kind of this challenge in solid tumors.