Yong-Chen William Lu, PhD
Results of a phase I dose-escalation study—the first clinical trial testing an immunotherapy that uses genetically engineered CD4 T-cells, rather than CD8 T-cells—demonstrate that the treatment could have potential in all metastatic tumor types, according to Yong-Chen William Lu, PhD.
In an interview with OncLive
, Lu, a fellow in the Surgery Branch of the National Cancer Institute, discusses a phase I dose-escalation study investigating the genetically engineered CD4 T cells' ability to target the MAGE-A3 protein, as well as the treatment's potential toxicities and currently ongoing responses in some patients still enrolled in the trial.
OncLive: Can you give us an overview of your study on CD4 T-cell immunotherapy targeting MAGE-A3 in multiple types of metastatic cancer?
: I presented the first CD4 genetically modified T-cell therapy against cancer. In this study, which was a first-line trial, we used different doses for the dose escalation to test different doses for the cell. We had 8 patients on dose escalation and another 6 patients on the highest dose, and for that we found 3 patients who responded to all therapy. One patient is a patient with cervical cancer, 1 patient with esophageal cancer, and another one with urothelial cancer. Those 3 patients are still showing an ongoing response and are doing well.
For this trial, we have 2 major questions. The first question is to test whether the CD4 T cell has the response to the cancer in most therapies, similar to CD8 T-cell therapy. The second question we wanted to ask is volume, because currently the cancer immunotherapy regimen has been to target melanoma, lymphoma, leukemia, and renal cell carcinoma, but the rest of the majority of cancers and those patients did not receive the benefit from that.
This trial tests the hypothesis that T-cell therapy can be applied to any type of cancer. We have been treating patients with melanoma, breast cancer, and cervical cancer. You could potentially apply this to many different types of cancer.
What are the next steps going forward?
Our major focus is in the phase II study. For the phase I study, we were confirming that this trial is safe and that we can use the higher dose to do that. In the phase II study, we are going to initially treat 20 patients, then up to 40 patients, for different cancer types. Our major focus will be in melanoma, cervical cancer, esophageal cancer, and urothelial cancer. Hopefully we will understand the effectiveness of this T cell therapy against different types of cancer.
What is the mechanism of action for this drug?
It's a very important, but very difficult question, because as we mentioned this is the first CD4 T cell therapy. We know very little about it. So far what we know is that the CD4 T cell is doing the job of helping the CD8 T cell. Other than that, we don't know much. We definitely have lots of work to do, both in humans and maybe mice studies. We hope that this trial will stimulate scientists to know more about the CD4 T cell and do more basic research toward the question.
What was the safety profile?
Thus far, the toxicities have been very mild. It's the same as all the other T-cell therapies; we have to use chemotherapy to clean out all the T cells that are in the patients, and that will create a space for our modified T cells to expand within the patient. Unfortunately, that is the same as other chemotherapies where you get the same side effects as a chemotherapy regimen.