A decade ago, Americans Bill Ludwig and Doug Olson They were battling a serious blood cancer called chronic lymphocytic leukemia (CLL). Both had received numerous treatments and, with few other options, volunteered to become the first participants in a clinical trial of an experimental therapy underway in the Abramson Cancer Center and the University of Pennsylvania (UPenn) Perelman School of Medicine.
Analysis of these two patients shows the highest persistence of CAR T-cell therapy recorded to date against leukemia
The therapy designed in this trial to eradicate these terminal phase leukemias is based on the so-called chimeric antigen receptor (CAR) T cells. These genetically modified cells to attack tumors are a living medicine made for each patient from her own cells.
The analysis of these two patients published in the journal naturee by UPenn researchers and their colleagues at Children's Hospital of Philadelphia shows the greatest persistence of CAR T-cell therapy recorded to date against leukemia.
CAR T cells have remained detectable at least a decade after infusion, with sustained remission in both patients. Jan Joseph Melenhorstfirst author of the article and researcher at UPenn, in a telematic press conference organized by the journal.
long term remission
"This long-term remission is remarkable, and seeing patients live cancer-free is proof of the tremendous potential of this 'living drug' that works effectively against cancer cells," added Melenhorst.
This long-term remission is remarkable, and to see patients living cancer-free is proof of the tremendous potential of this living drug.
Jan Joseph Melenhorst, UPenn
CLL, which is the first cancer in which CAR T cells were studied and used in an American university, is the most common type of leukemia in adults. Although treatment of the disease has improved, it remains incurable with standard approaches. Over time, patients can become resistant to most therapies, and many continue to die, the center said in a statement.
Doug Olson was diagnosed with this disease in 1996, as he himself commented at the press conference of Nature, and Bill Ludwig in 2000. By 2010, their cancers had mutated and were no longer responding to standard treatment. But as pioneers in the use of CAR T cells, they both achieved a complete remission that year.
Olson, a retired pharmaceutical industry researcher, is still running and has completed six half marathons. He also raises funds for the Leukemia & Lymphoma Society and helps newly diagnosed patients.
For his part, after his treatment, Ludwig, a retired corrections officer, toured the US with his wife in a motorhome and celebrated events with his family, including the arrival of new grandchildren. But sadly, in early 2021, he passed away due to complications from COVID-19.
The potential of CAR T cells
The authors note that until now little was known about the potential and long-term stability of the infused cells. In this analysis, the researchers observed an evolution of CAR T cells over time, with the appearance of a population of highly activated CD4+ cells that became dominant in both patients.
The researchers observed an evolution of CAR T cells over time, with the appearance of a population of highly activated CD4+ cells
The data indicate two distinct stages of responses to CAR T cell therapy in these patients, with an initial phase dominated by killer T cells and a long-term remission controlled by CD4+ T cells.
In the years that followed, these CD4+ cells continued to demonstrate characteristics of tumor cell killing and continued proliferation, which is a hallmark of CAR T cell efficacy against cancer: their strong ability to survive and thrive within the body, the authors explain.
For its part, David L Porter, Director of Cell Therapy and Transplantation at UPenn and co-author of the work, comments that “CAR T cell therapy has been extremely effective for specific leukemias and lymphomas. We look forward to continuing to work on these cancers, while also investigating their impact on solid tumors, which could lead to further development in this area in the coming years."
Porter emphasizes that something is always learned from each patient treated. “Both Bill and Doug have given us many leads that keep us focused on the next generation of personalized therapies,” she concludes.