Interview with Carl June, University of Pennsylvania, PMWC 2019 Honoree: The Driving Force Behind The First FDA Approved Gene Therapy – Kymriah

Dr. Carl June studies mechanisms of lymphocyte activation that relate to immune tolerance and adoptive immunotherapy for cancer and chronic infection. In 2011, his research team published findings detailing a new therapy in which patients with refractory and relapsed chronic lymphocytic leukemia were treated with genetically engineered versions of their own T cells, CAR-Ts. The treatment has also now been used with promising results to treat children with refractory acute lymphoblastic leukemia. His work led to the development and commercialization of tisagenlecleucel, the first FDA-approved gene therapy. In the 1980s, his lab discovering the CD28 molecule as the major control switch for T cells. Read his full bio.

Interview with Carl June, University of Pennsylvania, PMWC 2019 Honoree: The Driving Force Behind The First FDA Approved Gene Therapy – Kymriah

Q: The track theme is on the topic “How do we accelerate and deliver on the promise of cancer immunotherapy?” What are some key promises regarding immune-oncology, that we can build upon and translate into reality and how can we expedite delivery?

A: The use of the immune system to fight cancer holds a promise as a general solution to cancer therapy. At this point there are about 600,000 deaths every year in the United States from cancer in about 10% of those are from blood cancers and the other 90% from solid tumors

The key issues are how to raise the response rate from currently 20% in most cancers so that nearly everyone responds? This is a daunting challenge because of the diversity of different kinds of tumors. The tumor microenvironment is extremely complex and varies from patient to patient and even within patients, different metastasis can have major differences in the nature of the tumor microenvironment.

Q: What are some of the difficulties of clinical implementation of cancer immunotherapy and how can we overcome them?

A: There are number of issues and challenges with the implementation of new therapies. A major issue is that the tumor needs to be more precisely diagnosed. This has traditionally been done by pathologists and a microscope. Nowadays, a tumor needs to be fully characterized by sequencing at the DNA and RNA levels. At this point this can be done, but only a minority of patients have their tumors fully characterized. The technology to do this is just becoming generally available however there are numerous bioinformatic challenges that have not been solved.

Q: You have been working on CAR-T cells to treat B-cell acute lymphoblastic leukemia. What were some of the challenges you needed to overcome to make CAR-T cell therapy a reality?

A: Well as of 2018 CAR T-cell therapy is a reality! It was approved by the US FDA in August 2017. The challenges faced by CAR T Cell therapies are like many of those when a new industry is launched. At this point there are infrastructure issues in that the manufacturing centers need to be established to make the complex logistics less challenging.

The major issue we faced with the launch of CAR T-cell therapy was to convince the biotechnology and pharmaceutical industries that this could be a new modality of therapy. There has never been an ultra personalized therapy such as CAR T Cell therapies. Perhaps the most closely related process is bone marrow transplantation, and this is something that the pharmaceutical industry has not traditionally been engaged in developing. New forms of bone marrow transplantation have been developed by academic centers and not the pharmaceutical industry.

Q: What will next generation immunotherapies to treat cancer look like?

A: The next generation of immunotherapies need to be curative. A major problem with many of the current therapies is that they convert cancer into a chronic disease. Patient would rather be cured rather than have a chronic disease, although this is much better than the alternative which has been previous to immunotherapy, the rapid progression and death of most patients! But the realization that patients now live longer with cancer has caused a major emerging issue of financial toxicity. The recurrent cost of current immunotherapies and targeted therapies is not sustainable. In the past when patients rapidly died, the cost per patient was much less! So affordability has emerged as the major issue in the next generation therapies: they need to be curative rather than converting cancer into a chronic disease. The average annual cost of new cancer therapies that were approved by the FDA in 2017 was $150,000 per year.

Q: What is required to make breast cancer amenable to immunotherapy? Do you believe an immunotherapy-like approach to treat breast cancer is in the future?

A: There is exciting progress in the treatment of breast cancer with immunotherapy therapy. At a recent conference (ESMO 2018), the combination of chemotherapy and immune checkpoint therapy caused responses in approximately one-third of patients with triple negative breast cancer, the worst form of breast cancer.

Q: What else is important in the context of where we are in accelerating adoption of immune-oncology? Where do you see relevant themes in the context of the upcoming PMWC 2019 Silicon Valley conference?

A: Precision Medicine is evolving rapidly. It is important that the research, medical, and pharma communities collaborate to maintain momentum to accelerate progress so that we are able to deliver cutting-edge care and clinical trial opportunities to all patients. This requires the integration of diverse new technologies including bioinformatics, genetic editing, and cellular immunotherapy, to name a few. It is critical that the medical research community communicate effectively with congress so that prioritization at medical research remains at a high level. We are at the threshold of major advances for cancer therapy, however they will not be realized unless there is continued and coordinated research at the federal level.

Q: Is there anything else you would like to share with the PMWC audience?

A: We need to take great care not to overhype the progress that we’ve had: this is really just the end of the beginning.