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The Future of Melanoma Treatment May Be Complex, But 'Where There's a Will, There's a Way'


Research in the melanoma space is finding itself facing complex challenges in implementing CAR-T cell therapy, but according to one expert these challenges are not insurmountable.

As the treatment landscape for melanoma continues to evolve, scientists will likely focus more on the logistics of T-cell therapies and how to deliver them effectively across many modalities, according to Dr. Jason Luke, director of the Cancer Immunotherapeutics Center at UPMC and the University of Pittsburgh.

Recently, Luke spoke with CURE®’s sister publication, OncLive®, about what the future holds for the melanoma treatment landscape, and what kind of role T-cell therapy plays in that space. And while the complexity of these new treatments will become a factor, Luke explained, “Where there's a will there's a way, and when treatments work, we find a way to do it.”

OncLive: Can you start with discussing what you think the futures of T-cell therapy and melanoma look like, in your opinion?

Luke: In metastatic melanoma we've had a breakthrough with immune checkpoint blockade as a kind of immunotherapy, but also on the near-term horizon is the use of cellular therapies based on T-cells, and that really comes in two flavors.

The immediate is going to be the harvest of tumor infiltrating lymphocytes (TIL), and then building them up in the lab and giving them back to patients as a therapeutic modality. So in the refractory disease setting, there's already been a phase two clinical trial that has registration intent, in fact, showing that in patients who are progressed on everything, if you can harvest the tumor by surgery, grow these cells up in the lab, then give them back the patient, upwards of 40% of patients, again in the completely refractory disease setting, can have a response. So, it's very likely that therapy is going to be approved by the FDA, and I think that's really going to become part of standard practice moving into the future.

Further out is using engineered cells. Those can be T-cell-directed therapies in which we actually insert a T-cell receptor into T-cells from the patient, as well as chimeric antigen receptor T-cells, where we actually drive a T-cell with an enhanced antigen, that drives itself to go after the cancer. I think the latter two are actually further out in terms of treatment modalities, but certainly T-cell based therapies are on the near horizon.

What steps needs to be taken over the next five years, for example, to make the best use of T-cell therapy?

So, as T-cell therapies come into standard practice, we really have to think about what the infrastructure is going to look like in order to actually pull off these kinds of treatments. Again, the complexity is much greater than say, infusing a drug in an outpatient setting, because for TIL therapy, patients undergo surgery, that tumor has to be processed adequately in the lab, it needs to be usually shipped out to a vendor and then shipped back. The patient has to be brought into the inpatient setting to begin chemotherapy prior to the TIL (therapy). There are a lot of moving pieces here that will be different than the usual ambulatory practice.

And then as we think further out about other T-cell based therapies like TCR based T cells or CAR T-cells, that again introduces this complexity where we actually have to bring large volumes of white blood cells out of a patient, transduce those T-cells in the lab, and then give them back to patients. So again, a multi-modality treatment that requires both an inpatient component and outpatient component and quite a bit of laboratory complexity. But I would say that, where there's a will there's a way, and when treatments work, we find a way to do it.

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