Optimizing leukapheresis product yield and purity for blood cell-based gene and immune effector cell therapy

A critical common step for blood-based ex-vivo gene and immune effector cell (IEC) therapies is the collection of target cells for further processing and manufacturing, often accomplished through a leukapheresis procedure to collect mononuclear cells (MNCs). The purpose of this review is to describe strategies to optimize the apheresis product cell yield and purity for gene and IEC therapies. Relevant data from the conventional bone marrow transplant literature is described where applicable.

Product yield is affected by three main factors: the peripheral blood concentration of the target cell, optimized by mobilizing agents, donor interventions or donor selection; the volume of peripheral blood processed, tailored to the desired product yield using prediction algorithms; and target cell collection efficiency, optimized by a variety of device and donor-specific considerations. Factors affecting product purity include characteristics of the donor, mobilizing agent, device, and device settings.

Strategies to optimize product yield and purity for gene and IEC therapies are important to consider because of loss of target cell numbers or function with downstream steps and detrimental effects of nontarget cells on further manufacturing and patient outcome.