Glioblastoma multiforme (GBM) is the deadliest form of brain cancer, with a median survivorship of just 14 months, even with gold-standard therapy. Currently, there are limited effective treatment options for this disease, especially in cases of relapse.
To address this gap, the Empirica team has validated CD133, an established marker of cancer stem cells, as a promising therapeutic target for recurrent GBM. Using high affinity CD133 antibodies, Empirica has engineered second-generation chimeric antigen receptor (CAR)-T cells that have successfully eliminated treatment-resistant tumours in unique models of GBM recurrence.
A CAR is a transmembrane receptor that is engineered by fusing an extracellular antibody fragment (single-chain variable fragment or scFv), specifically recognizing a tumour antigen, to the intracellular activation domain of a T-cell receptor. Unlike natural T-cell receptors, CARs can recognize antigens independently of processing and presentation. The antigen-specific scFv is ideally directed to cell type-specific molecules like CD19 for B cell malignancies, or to tumour-specific antigens like CD133 for GBM. Additional elements of the CAR enhance T-cell persistence and expansion at the tumour site. Currently, most commonly used protocols for CAR-T therapy involve engineering patient-derived T cells to express the CAR on their cell surface, followed by in vitro expansion and re-implantation (autologous CAR-T therapy) in the patient.
Empirica is further developing the eCAR-133 toward clinical trials.
The company is also using its robust platform to identify additional targets that can broaden applications of the therapy to brain tumours and other cancers. Empirica has the ability to create multiple modalities of treatments, which will widen their applicability.
Additional products in Empirica’s pipeline will be developed through collaborations or strategic partnerships that complement the expertise built within Empirica.