Researchers said Wednesday they created a second-generation chimeric antigen receptor (CAR) T-cell therapy that prevented relapse of lymphoma and leukemia and led to 100% long-term survival in early laboratory studies.
Researchers said Wednesday they created a second-generation chimeric antigen receptor (CAR) T-cell therapy that prevented relapse of lymphoma and leukemia and led to 100% long-term survival in early laboratory studies.
Trials in human participants are expected to begin within 6 months, according to one of the researchers involved in the study, which was published in Science Translational Medicine.
The research was led by City of Hope and also involved scientists from universities and medical centers in China as well as the University of Southern California and Weill Cornell Medical College.
There is a 30% chance of relapsing with the 2 CAR T therapies on the market, Novartis’ tisagenlecleucel, sold under the name Kymriah, and axicabtagene ciloleucel, or Yescarta, from Kite Pharma/Gilead. Those 2 products attack the target antigen CD19, but in some patients, relapse occurs when the lymphoma cells stop producing CD19.
This second-generation of CAR T targets an alternative surface marker called B cell activating factor receptor (BAFF-R). Scientists engineered CAR T cells to go after human lymphoma and acute lymphocytic leukemia cells expressing BAFF-R in vitro and in mouse models in comparison with CD19-directed CAR T cells.
The BAFF-R-CAR T cells also killed CD19-negative tumor cells isolated from 4 patients with leukemia who relapsed after being treated with a CD19-targeting antibody, and extended survival in mice that were implanted with cells from a fifth relapsed patient. In addition, the BAFF-R-directed CAR T cells targeted CRISPR-modified human leukemia cells that lacked CD19.
More experiments will be needed to confirm whether tumor cells could potentially evolve resistance by losing BAFF-R, the rights to which are owned by California biotech Pepromene Bio, but for now, the BAFF-R is being eyed as a viable target for CAR T cell treatments.
“This new treatment offers hope for patients whose tumors have returned after initially successful CAR T-cell therapy, a currently unmet need,” said Larry Kwak, MD, PhD, the vice president and deputy director at the Comprehensive Cancer Center at the City of Hope, in an email to The American Journal of Managed Care®. “If successful, it could ultimately be used as initial, frontline treatment and thereby change the face of leukemia and lymphoma therapy globally.”
He said the upcoming clinical trial is planned for adult patients with acute lymphoblastic leukemia whose tumors have relapsed after treatment with Yescarta and Kymriah, as well as Blincyto, another form of immunotherapy.
Reference
Qin H, Dong Z, Wang X, et al. CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies. [published online September 25, 2019]. Sci Transl Med. doi: 10.1126/scitranslmed.aaw9414.