PeproMene Bio Unveils Study on Novel CAR T Cells' Strong Polyfunctionality

PeproMene Bio, Inc., a clinical-stage biotechnology firm based in Irvine, California, has announced promising results from a study on their novel BAFF-R CAR T cell therapy, known as PMB-CT01. The study, conducted by researchers at City of Hope, revealed that PMB-CT01 exhibits superior polyfunctionality compared to the currently FDA-approved CD19 CAR T cell therapies. This research has been published in Blood Advances.

The study utilized a single-cell platform to analyze PMB-CT01 CAR T cells and found that they exhibit a higher degree of polyfunctionality— the ability of T cells to perform multiple functions simultaneously—than CD19 CAR T cells. Additionally, PMB-CT01 cells were noted to produce more stimulatory and effector cytokines, which respectively aid in activating the immune system and directly destroying cancer cells.

Researchers tested a BAFF-R CAR T cell product on a 57-year-old man suffering from relapsed mantle cell lymphoma. This patient had previously not achieved remission with CD19 CAR T cell therapies. After a single infusion of PMB-CT01 in a Phase 1 trial at City of Hope, the patient experienced minimal side effects and has been in complete remission for over 18 months. Molecular tests for minimal residual disease have shown that his cancer remains undetectable.

The study's findings indicated robust indicators of polyfunctionality, which correlated with successful post-infusion CAR T cell expansion and the patient's continued remission. Future plans include using this assay to evaluate CAR T cell products from five additional trial patients who have shown similar positive responses to PMB-CT01.

Dr. Larry W. Kwak, vice president and deputy director of City of Hope's Comprehensive Cancer Center and PeproMene's scientific founder, emphasized BAFFR-CAR T therapy as a new treatment alternative for patients with lymphomas and leukemias who relapse after commercial CD19 CAR T cell therapy. Kwak highlighted the ideal combination of maximal efficacy and minimal toxicity achieved so far and mentioned the development of a reliable polyfunctional assay to predict patient outcomes and accelerate effective CAR T cell therapies.

Dr. Elizabeth Budde, the trial's principal investigator and a professor of hematology and hematopoietic cell transplantation at City of Hope, presented the initial trial results at the American Society of Hematology's conference in December 2023. She reported that all six patients treated—five with non-Hodgkin lymphoma and one with B-cell acute lymphoblastic leukemia—demonstrated durable responses to PMB-CT01. These patients had either relapsed after CD19 CAR T therapy or were CD19 negative, suggesting that PMB-CT01 could be an effective alternative for similar future cases.

Dr. Hazel Cheng, COO of PeproMene Bio, stated that this assay could be used in current and future clinical trials to further the development of PMB-CT01. The company remains committed to advancing this promising new cell therapy.

PMB-CT01 is a first-in-class, BAFF-R-targeted, autologous CAR T cell therapy. BAFF-R, a member of the TNF receptor superfamily, is predominantly expressed on B cells. Since BAFF-R signaling is crucial for B-cell proliferation and survival, tumor cells are unlikely to evade therapy through loss of the BAFF-R antigen. This makes BAFF-R CAR T therapy a highly promising option for treating B-cell malignancies. The BAFF-R CAR was created using anti-BAFF-R single-chain fragment variable (scFv) antibodies and second-generation signaling domains CD3ζ and 4-1BB. Research has shown that BAFF-R CAR T cells can effectively kill human lymphomas and leukemias in both laboratory and animal models. PeproMene Bio has licensed the intellectual property of PMB-CT01 from City of Hope.

PeproMene Bio is developing innovative therapies for cancers and immune disorders, with PMB-CT01 currently being tested in Phase 1 clinical trials for relapsed B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma. The company is also working on BAFF-R Bispecific T Cell Engager and BAFF-R CAR NK cells.