fbpx
Subscribe
Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors

Advertisment

Preliminary results of gene-based immune therapy in ALL

Written by | 1 May 2013 | All Medical News

Researchers reported encouraging but preliminary results of gene-based immune therapy in two children with relapsed and refractory acute lymphoblastic leukemia (ALL).

Both children achieved a remission after they were given T cells modified to attack B cells bearing the surface protein CD19, according to Stephan A. Grupp, MD, PhD, of the Children’s Hospital of Philadelphia, and colleagues.

One child remains in remission after 11 months, but the other suffered a relapse when cancerous B cells that did not have the CD19 marker appeared, Grupp and colleagues reported online in theNew England Journal of Medicine.

The study shows that the modified T cells “have a potent anti-cancer effect in children” with ALL, Grupp said in a statement. “However, we also learned that in some patients with ALL, we will need to further modify the treatment to target other molecules on the surface of leukemia cells.”

So-called chimeric antigen receptor-modified T cells — targeting the antigens CD19 and CD20 — have been reported to be effective in adults with chronic lymphoid leukemia and B-cell lymphomas, the researchers noted.

But it had not been clear if the modified T cells would multiply in patients with ALL, which is a less mature leukemia that progresses more rapidly, or if they would work in patients who had relapsed or who had high tumor burdens or both.

To help clarify the issue, Grupp and colleagues used the method to treat two children with relapsed and refractory ALL — a 7-year-old girl who had relapsed twice and was not responding to intensive chemotherapy and a 10-year-old girl who also had relapsed twice and was not responding to antibody therapy targeting the CD19 antigen.

In both girls, T cells were extracted and transduced with an anti-CD19 antibody and a T-cell signaling molecule. The resulting cells – dubbed CTL019 chimeric antigen receptor T cells – were then re-infused at doses of between 1.4×106 to 1.2×107 cells per kilogram of body weight.

The CTL019 T cells expanded by a factor of more than 1,000, and cells were found in bone marrow and in the cerebrospinal fluid. Both girls had a complete remission, Grupp and colleagues reported, but the older girl relapsed 2 months after treatment, with B cells that did not express the CD19 antigen.

In the days after treatment, both girls suffered grades 3 and 4 adverse events. Specifically:

  • The younger girl had grade 3 neutropenia, grade 4 hypotension that was regarded as life-threatening, grade 4 acute vascular leak syndrome that was also seen as life-threatening, and grade 4 acute respiratory distress syndrome that required intubation.
  • The older patient had grade 3 febrile neutropenia and encephalopathy, as well as grade 4 elevations of both alanine aminotransferase and aspartate aminotransferase.

The study is part of a collaboration with researchers, led by Carl June, MD, of the University of Pennsylvania, who pioneered the use of chimeric antigen receptor-modified T cells in the treatment of B-cell leukemias.

The goal is to use the approach to “reduce or even replace the need for bone marrow transplants, which carry a high mortality risk and require long hospitalizations,” June said in a statement.

“If the treatment is effective in these late-stage patients, we would like to explore using it up front, and perhaps arrive at a point where leukemia can be treated without chemotherapy,” he added.

June and colleagues have also experimented with modifying T cells as a way of treating HIV.

The study was supported by the NIH and the Leukemia and Lymphoma Society. Grupp reported holding patents on toxicity management. Senior author Carl June, MD, reported financial links with CellDex, Immune Design, Cerulean Pharma, Novartis, and Kadmon. He also has patents for cell culture technology and chimeric antigen receptor technology.

Reference:
Grupp SA, et al “Chimeric antigen receptor–modified T cells for acute lymphoid leukemia” N Engl J Med 2013; DOI: 10.1056/NEJMoa1215134.

Newsletter Icon

Subscribe for our mailing list

If you're a healthcare professional you can sign up to our mailing list to receive high quality medical, pharmaceutical and healthcare E-Mails and E-Journals. Get the latest news and information across a broad range of specialities delivered straight to your inbox.

Subscribe

You can unsubscribe at any time using the 'Unsubscribe' link at the bottom of all our E-Mails, E-Journals and publications.