T cells

Differentiation states (from least to most differentiated)

1. Naive: never encountered antigen, best for cell therapy, high proliferative capacity after encountering its target
2. Central memory: has encountered antigen but still multipotent, good proliferative potential
3. Effector memory: more specialized, less proliferative capacity
4. Terminal effector: end-stage cells, limited lifespan, poor therapeutic potential

Differentiation states’ impact on T cells’ therapeutic potential in cell therapies

• Less differentiated (naive/central memory) make better cell therapies bc
  • Better persistence (longer lifespan)
  • Higher proliferative capacity
  • Better anti-tumor activity
• Manufacturing processes can stress cells, pushing them toward terminal differentiation
  • Electroporation appears to drive terminal differentiation, whereas PERC is gentler on cells, maintaining more desirable less-differentiated states (source)

How to determine T cell differentiation state: staining T cell surface markers

• stain T cells with antibodies against cell surface markers (e.g. CD45RA, CCR7, etc.)—which are expressed at different levels depending on differentiation state