Takeaways

1.

Efficacy is diminished due to the predominance of more differentiated cells in the final CAR-T product

Identification of various differentiated subpopulations results in the ability to optimize the CAR-T manufacturing process

2.

The actionable insights provided by Immunomind assist when selecting the most effective composition of a CAR-T product, and allow modification of the manufacturing process

3.

Background

Those properties are directly associated with the differentiation status of the product. After being introduced to the antigen, naive T cells can differentiate into effector and memory cells. Terminal effector memory T cells have high lytic antitumor activity , but are limited by low proliferation and persistence properties. A less differentiated subpopulation of memory T cells has enormous proliferative potential. This provides excellent possibilities for long-term persistence in vivo, and may give rise to other subpopulations. These properties make less differentiated cell subpopulations the best candidate for application in CAR-T therapy.

The anti-tumor capability of CAR-T cells, as well as the frequency of remissions, depend on the degree of proliferation, persistence, and survival of those CAR-T cells.

Problem

Efficacy of a therapy is decreased by the predominance of more differentiated cells in the final CAR-T product

The level of differentiation within CAR-T cells is a pivotal property in the manufacture of an infusion product. When T cell subpopulations become more differentiated, the chance for the CAR-T drug to trigger tumor regression declines profoundly. As a result, CAR-T manufacturing requires the selection of CAR-T cells with a suitable differentiation status, accompanied by the prevalence of less-differentiated subpopulations such as:
• T naive (Tn)
• T stem cell memory (Tscm)
• T central memory (Tcm)