Lymphodepleting chemotherapy in order to safely improve the expansion of HER2-CAR T cells in patients with advanced sarcomas

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Published: 15 Apr 2019
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Prof Shoba Navai - Baylor College of Medicine, Houston, USA

Prof Shoba Navai speaks to ecancer at the 2019 American Association for Cancer Research (AACR) meeting about results from a study looking at lymphodepleting chemotherapy in order to safely improve the expansion of HER2-CAR T cells in patients with advanced sarcomas.

She explains that the study succeeded in safely doing this with very limited toxicities seen and no cardiac toxicities which can be seen in other HER-2 directed therapies.

Prof Navai reports that the addition of lymphodepletion did help improve CAR T cell expansion in the blood and that there are early signs that endogenous immunity may be engaged when administrating the CAR T cells.

Read more about this research here.

This morning I discussed the results from our ongoing phase I clinical trial testing HER2-CAR T-cells in combination with lymphodepletion chemotherapy for patients with advanced sarcomas. The primary purpose of the study as it was a phase I study was to determine the safety of doing this and we did see that we had very limited treatment related toxicities and, importantly, no cardiac toxicities which can be seen with other HER2 directed therapies. The addition of lymphodepletion did help us improve our CAR T-cell expansion in the blood and we were fortunate to have patients with responses. So we had two patients who developed complete responses that have been maintained over a longer period of time. We have some early signs based on some immune correlative work that endogenous immunity may be engaged when we administer these CAR T-cells and so that’s exciting to us that we are getting secondary benefits from the CAR T-cells.

What are the next stages in this research?

The next stages forward in our work are, first, to identify other tumour targets because we think that because solid tumours are heterogeneously expressing different proteins that it may be important to target multiple things. Another thing is to consider using this approach in combination with other approaches such as checkpoint inhibitor blockade as this might help the CAR T-cells function and persist for longer in the body.

Do you think this work could further expand into other avenues?

We do think that this approach might be applicable to other tumour types and we are looking forward to expanding this type of treatment to patients with other types of HER2 expressing solid tumours.

Is this something you are pursuing as a team and with a multidisciplinary approach?

Research of this type requires a large number of people to be involved, from the people designing the study to the patients we are recruiting to our GNP facility. This type of approach can take a long time to develop things and so we do hope that at some point in the future that CAR T-cell therapies for solid tumours will become more accessible to more patients as some of them are showing early signs of efficacy but we are a ways off from that.

What are some of the barriers that need to be broken before it can become more accessible?

Some of the barriers that are there that might make it more difficult for this to be generalisable to a larger number of patients, one is the cost of CAR T-cell manufacturing. Our CAR T-cell in the lab is a limited treatment cost but when it gets transferred into a company setting, as in the case of CD19 CAR T-cells, it can become quite expensive. So bringing down the cost will be very important. Secondly, we need to show that efficacy studies in a larger number of patients so that we can determine which patients might actually benefit from this treatment as not all patients respond.

Our research group from Baylor College of Medicine consists of a large number of people who contributed to this trial. Most importantly, Dr Meenakshi Hegde who is our lead on this trial and she designed this lymphodepletion cohort of the trial as well as the immune correlative work that was presented today. I would also like to acknowledge Dr Nabil Ahmed and Stephen Gottschalk who initially designed this trial without lymphodepletion and who continue to be involved in its success.