It was in 2010 when pioneering immunologist Carl June and his colleagues at the Abramson Cancer Center and Perelman School of Medicine at the University of Pennsylvania treated two patients with chronic lymphocytic leukemia (CLL) with CAR cells. -T targeted to CD19.

The two patients, Bill Ludwig and Doug Olson, had each volunteered to be the first participants in the phase I clinical trial of this new treatment. Both had already exhausted many other treatment options. At the time, both patients responded with complete remission of their CLL. Now, 12 years later, researchers from Penn and Children’s Hospital of Philadelphia have published an analysis of a decade-long study of these two patients. The new paper, published earlier this month in Nature, reported that both patients remained in remission a decade after their treatment and that CAR-T cells remained detectable in their bodies.

Given those decade-long remissions, scientists who had been involved in the research at Penn are now beginning to use the word “cure” in relation to CAR-T therapy.

The CAR-T therapy Ludwig and Olson had been treated with was developed in conjunction with Novartis and in 2017 became the first regulator-approved CAR-T therapy (now known as Kymriah). In the years that followed, we saw more CAR-T approvals (Yescarta from Gilead which was also approved in 2017 and Tecartus, approved in Europe in 2020). BMS’s Breyanzi has also received FDA clearance and is pending approval in Europe.

Despite these early successes and enthusiasm, CAR-T therapy currently only works for a small number of patients with specific types of blood cancer who have not responded to other treatments. However, given the dramatic results in blood cancers, much research is underway to develop next-generation CAR-T therapies.

There are currently over 500 CAR-T trials underway worldwide.

Challenges researchers are trying to address include trying to tailor the treatment to work with solid tumors, controlling toxicity and improving targeting of cancer cells rather than healthy cells, shielding cells to reduce “burnout” (when CAR-T cells stop working over time) and using allogeneic (donor cells) rather than autologous (patient cells) treatments.

If you want to read more about cell therapies (including an introduction to cell therapies and their regulation, a discussion of regulatory T cell therapies, and current issues affecting viral vectors), check out Bristows’ Biotech journal, available for download here: https://www.bristows.com/publications/biotech-review/

Two of the first human patients to be treated with a breakthrough therapy that engineers immune cells to target specific types of cancer still have cancer killer cells a decade later with no signs of their disease returning.

The finding suggests that CAR T-cell therapy is a “cure” for some blood cancers, although adapting it to treat solid tumors is proving more difficult.

https://amp.theguardian.com/society/2022/feb/02/first-patients-pioneering-car-t-cell-therapy-cured-of-cancer