Method for Assessing Out-of-Specification (OOS) CAR T-Cell Products and Predicting Patient Response

Reference Number TO 32-00128

Keywords

CAR-T cell therapy, CD19, prognostic biomarkers, therapy response, out-of-specification (OOS) CAR T-cell products

Invention Novelty

This innovation presents a novel diagnostic approach for predicting the therapeutic response of patients subjected to CD19-chimeric antigen receptor (CAR)-T cell therapies utilizing a novel combination of predictive biomarkers. Developed as part of a clinical study, with third-generation CAR-T cell products, the researchers identified the expression of CD39 and CD27 to be directly associated with therapy response. This biomarker combination offers the capability to evaluate out-of-specification (OOS) CAR-T cell products by determining whether a sufficient absolute number of therapeutically effective CAR-T cells is present (Fig. 1).

Value Proposition

This biomarker combination provides a rapid, cost-effective method for quantifying therapeutically active CAR-T cells, making it a valuable tool for quality control and clinical decision-making. It enables reliable prediction of patient response to CAR-T therapy and supports personalized treatment selection. The assay is especially advantageous when only limited starting material is available such as with OOS CAR-T cell products. By enabling data-driven treatment decisions and reducing the risk of ineffective therapies, this innovative assay could broaden patient access, lower costs associated with OOS products and help shape future regulatory standards.

Fig 1. The absolute number of therapeutically effective CAR-T cells determines therapy response

Technology Description

Flow cytometry analysis of CAR-T cell infusion products revealed that CAR-T cells bearing a CD39- and CD27- phenotype are strongly associated with good clinical response. While CD39 denotes exhausted or dysfunctional T cells, the absence of CD27 indicates a higher effector capacity. In combination, these markers represent functional effector or effector-like T cells and can thus be used to determine the number of therapeutically effective CAR-T cells in the product. Crucially, these two markers can be measured with any standard FACS instrument, enabling rapid and low-cost evaluation of CAR-T cell batches.