Addressing High Relapse Rates in CAR T-Cell Therapy


Paul Rennert, president and chief scientific officer of Aleta BioTherapeutics, discussed the company’s CAR T Engager protein technology.

"Half of [patients] then relapse, and they relapse quickly. We recognized... that they were relapsing because their target cancer cells are losing antigen expression. So, for CD19+ lymphoma, the patient's lymphoma cells simply downregulate the target... [We created] a class or a platform of assets that we call CAR T Engager proteins designed to link a CAR T-cell to multiple antigens simultaneously, thereby preventing loss of response to any single antigen.”

While chimeric antigen receptor (CAR) T-cell therapy has certainly made strides in treating B-cell malignancies and multiple myeloma, there is still work to be done in improving these therapies, particularly in improving the high relapse rates seen in patients treated with CAR T-cell therapy. Aleta BioTherapeutics hopes to improve relapse rates with the use of their CAR T Engager proteins that are designed to address target cells’ loss of antigen expression.

The company’s lead program, ALETA-001, is a CD20 targeted CAR T Engager designed to treat patients with hematologic malignancies relapsing after CD19 CAR T therapy and is currently in investigational new drug-enabling studies. Other programs in hematologic malignancies and solid tumors are earlier in the pipeline.

GeneTherapyLive spoke with the company’s president and chief scientific officer, Paul Rennert, to learn more about their CAR T Engager proteins. He also discussed ALETA-001 and the ALETA-004 program targeting adult acute myeloid leukemia, myelodysplastic syndrome, and chronic myelomonocytic leukemia.

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