WIB-Seattle: Cell Therapies in Practice in Seattle

The panel discussion was held on September 16 at the Bristol Myers Squibb office in South Lake Union.  Heidi LeBlanc, a WIB-Seattle Programs volunteer, welcomed everyone to the event and thanked our sponsors before introducing Katie Newhall, WIB-Seattle's EWIB Committee Co-Vice Chair, who moderated the panel. After she introduced the panel of speakers, which included Dr. Aude Chapuis of Fred Hutch, Dr. Leanna Peiser of BMS, and Dr. Blythe Sather of Tune Therapeutics, Katie provided a succinct explanation of cell therapy—a process by which a patient's immune cells (T cells) are extracted and then genetically modified to fight cancer. She explained that this approach is especially effective for hematologic cancers, such as types of lymphoma or leukemia. Katie mentioned that since the first chimeric antigen receptor T cell (CAR-T) therapy was approved in 2017, the challenge has been expanding this type of treatment beyond hematologic cancers.

From there, the first question posed to the panelists was about whether different types of cells can be used for a similar approach as CAR-T therapy. Dr. Aude Chapuis spoke about how the reason that CAR-T works is that there is a high density of the surface proteins that the CAR-T cells target and the challenge is to find another type of surface protein that is specific enough to a solid tumor that the modified T cells won't also attack normal body tissue. Research is being done to identify tumor-specific mutations, but there is also a challenge with increasing the potency of T-cell therapy without also increasing the toxicity.

Dr. Blythe Sather spoke about how patients who have already received several lines of therapy before CAR-T therapy have difficulties due to cell exhaustion. She said that there is a lot of interest in a "universal, off-the-shelf" type of therapy, where the industry can decrease the amount of time spent on genetically modifying the T cells and get treatments to patients faster.

Dr. Leanne Peiser stated that there is a lot of interest in using an in vivo approach to T-cell therapy because that would reduce the need to remove cells and modify them ex vivo. However, this approach presents a challenge because it is difficult to target the correct cells and not unintentionally edit off-target cells. In addition, research is being done to see if other types of cells, such as natural killer (NK) cells, could be successful.

Katie's next question was about how to apply T-cell therapies to indications beyond oncology. All panelists expressed their excitement about expanding this type of therapy into autoimmune diseases like lupus. Currently, treatments for autoimmune diseases are repeated many times over a patient's life, but T-cell therapy presents an opportunity for a "one-and-done" treatment. However, expansion into this space is still very early, and researchers are trying to determine which diseases to target.

Another question that came up was what the biggest challenge is with CAR-T therapy. Dr. Blythe Sather responded that the biggest challenge that she sees is convincing a regulatory authority to expand this type of treatment beyond hematologic oncology applications. Since it's such a new type of therapy, it is difficult to write the book on which patients to target and how successful this treatment might be. Dr. Aude Chapuis pointed to the expense of CAR-T therapy, where manufacturing alone may cost a CAR-T project almost 90% of its budget. Dr. Blyther Sather said that she sees a big challenge with the overlooked diseases that could benefit from this type of therapy. A lack of investment means that diseases that very well could respond amazingly well to this approach simply aren't getting the funding.

Finally, Katie asked what is the most exciting thing about CAR-T cell therapy. Everyone said that they are very much looking forward to expanding this type of therapy into new indications and finding ways to treat life-long diseases that have previously been difficult to manage. Katie said, "Moving beyond oncology is really exciting, especially beyond just hematologic indications. Regarding solid tumors and autoimmune diseases, the in vivo approach presents an opportunity for something absolutely transformative."

Devon Fitzgerald shared that she attended this event because cell therapy is well outside her field, but she was interested in learning more. "Before this event, I hadn't heard anything about using cell therapy for other indications beyond heme. It's really exciting," she said. Kimberly Smythe, who works with Dr. Aude Chapuis at Fred Hutch, said she was amazed at how many technologies there are to identify why and how a treatment like CAR-T cell therapy works. "My question is, with all these new technologies, and given how expensive they are, how do people in academia keep up?"

What resonated the most with attendees was just how far beyond oncology CAR-T cell therapy can reach. Attendees were especially engaged during the portion of the panel that focused on autoimmune applications. Multiple people asked about the future of CAR-T cell therapy as a first-line treatment, and others asked about how CAR-T cell therapy can be expanded to reach a larger number of patients who may benefit greatly from it. Attendees came away excited about the new frontier and eagerly discussed the evening's topic after the panel concluded.

Submitted by Mariana Huben