Table 3.

Summary of advantages and disadvantages of the different strategies

VariantsAdvantagesDisadvantages
Coadministration 
  • Minimal optimization: allows for combination of 2 single CAR constructs

  • Dose can be adjusted for each single CAR product

 
  • High manufacturing cost

  • Coordination and regulation around 2 infusions of 2 different products

 
Cotransduction 
  • Minimal optimization: allows for combination of 2 single CAR constructs

 
  • High manufacturing cost

  • Heterogeneity in product composition may result in uneven expansion in vivo

 
Bicistronic vector 
  • Only 1 vector (lower cost)

  • Homogeneous product

  • Single activation signal

 
  • Large vector size can result in lower transduction efficiency

  • Impact of increased CAR density/signaling uncertain

 
Bivalent CAR 
  • Only 1 vector (lower cost)

  • Homogeneous product

  • Single activation signal

 
  • Optimization of construct to ensure efficient targeting of both antigens challenging

 
VariantsAdvantagesDisadvantages
Coadministration 
  • Minimal optimization: allows for combination of 2 single CAR constructs

  • Dose can be adjusted for each single CAR product

 
  • High manufacturing cost

  • Coordination and regulation around 2 infusions of 2 different products

 
Cotransduction 
  • Minimal optimization: allows for combination of 2 single CAR constructs

 
  • High manufacturing cost

  • Heterogeneity in product composition may result in uneven expansion in vivo

 
Bicistronic vector 
  • Only 1 vector (lower cost)

  • Homogeneous product

  • Single activation signal

 
  • Large vector size can result in lower transduction efficiency

  • Impact of increased CAR density/signaling uncertain

 
Bivalent CAR 
  • Only 1 vector (lower cost)

  • Homogeneous product

  • Single activation signal

 
  • Optimization of construct to ensure efficient targeting of both antigens challenging

 

Adapted from Cordoba et al49 and Xie et al.47 

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