- New gene therapy
shows promise as a therapeutic for treatment- resistant B-cell leukemia.
- The therapy
alters the patient's own immune cells to target a molecular marker called
- New prospects
include a gene therapy approach that targets both the CD19 and CD22
New gene therapy shows promise in treating
patients with treatment- resistant B-cell leukemia. The study conducted by
research teams at Stanford University School of Medicine and the National
Cancer Institute show that a significant number of children who were part of
the study achieved remission with the help of the new gene therapy. The
findings of the study are published in Nature Medicine.
resistant B-cell leukemia B-cell
acute lymphoblastic leukemia
is the most common cancer in children
is the standard treatment. However, there are groups of patients who do not
respond to chemotherapy. There are also groups of patients who experience a
relapse in the cancer after successful remission. This type of B cell leukemia
can be characterized as treatment resistant.
CD19-targeted chimeric antigen receptor T-cell
therapy, or CAR T-cell therapy is the original gene therapy that showed
promising results for treating treatment- resistant B-cell leukemia. This FDA
approved therapy modifies the patients T cells to target the molecular marker
CD19 expressed on the surface of cancer cells.
However, recent studies have shown that in
some patients who undergo CD19-targeted CAR T-cell therapy, their cancer cells
stop expressing the CD19 molecule on their cell surfaces. In fact 15 out of 21
patients who were enrolled in the treatment either relapsed or failed to
respond to the treatment.
CAR T-cell therapy: The new gene therapy
This therapy is similar to but distinct from
the anti-CD19 CAR T-cell therapy. The primary and key difference is in the
molecular marker it targets. The new therapy targets another key molecular
marker on the cell surface of cancer cells: CD22. This therapy modifies the
patient's own T cells, a type of immune cells, to kill cancer cells by training
them to recognize CD22 marker on the surface.
‘Anti-CD22 CAR T-cell therapy modifies the patient’s T cells by training it to target cancer cells that carry the CD22 cell surface marker.’
"This is the first time that we've seen
response rates anything like we achieved when we were first testing the CD19
CAR T therapy," said Crystal Mackall, MD, the associate director of
Stanford's Cancer Institute and the director of the Parker Institute for Cancer
Immunotherapy at Stanford. "We were all a little worried that we wouldn't
find anything comparable. But this study gives hope to the idea that there may
be another similar, very potent treatment."
The research team hopes to develop a therapy
that targets both the CD19 and CD22 markers—an approach the team believes the
cancer cells cannot evade.
Phase I study
The study enrolled patients aged 7 to 30 with
B cell acute lymphoblastic leukemia. The participants received varying doses of
the anti-CD22 CAR T-cell therapy and all of them had received at least one bone
marrow transplant. Moreover, 10 out of the 15 patients who previously received
the CD19 treatment no longer expressed CD9 on their cancer cells.
At the lowest dosage 1 out of 6 patients
achieved complete remission. At the next higher dosage 11 out of 15 achieved
remission. The median remission period was 6 months with 3 patients remaining
in complete remission at six, nine and 21 months after the therapy.
"The take-home message is that we've
found another CAR T-cell therapy that displays high-level activity in this
phase-1 trial," said Mackall. "But the relapse rate was also high. So
this forces the field to get even more sophisticated. How much of a target is
needed for successful, long-lasting treatment? What happens if we target both
CD19 and CD22 simultaneously?"
- Terry J Fry, Nirali N Shah, Rimas J Orentas, Maryalice Stetler-Stevenson, Constance M Yuan, Sneha Ramakrishna, Pamela Wolters, Staci Martin, Cindy Delbrook, Bonnie Yates, Haneen Shalabi, Thomas J Fountaine, Jack F Shern, Robbie G Majzner, David F Stroncek, Marianna Sabatino, Yang Feng, Dimiter S Dimitrov, Ling Zhang, Sang Nguyen, Haiying Qin, Boro Dropulic, Daniel W Lee, Crystal L Mackall. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nature Medicine, (2017);DOI: 10.1038/nm.4441