Next-generation CAR-T cell manufacturing strategies
| . | Pros . | Cons . |
|---|---|---|
| Accelerated cell manufacturing | •Reduced vein-to-vein time •Less resource intensive •Increased manufacturing capacity •Less differentiated T cells in final product •Potential for reduced T-cell doses | •Increased potential for contaminating tumor cells in product (particularly for hematological malignancies) •Potential for T cells having overly active phenotype, leading to increased toxicities •Complexity in product-release testing (e.g., inability to distinguish between transient protein expression from pseudo-transduction versus stable integration) |
| Process automation | •Reduced personnel and infrastructure costs •Reduced probability of human error •Potential for on-site manufacturing enabling fresh cell products | •Reduced capability to respond to patient-specific cell behaviors during manufacturing •Challenge in ensuring consistency across multiple sites for point-of-care manufacturing •Limited capacity to perform long-term release testing for fresh products |
| In vivo cell manufacturing | •Cost and time saving from eliminating need for ex vivo cell manufacturing •Potential for less differentiated T cells •Off-the shelf reagents instead of patient-specific products | •Potential genotoxicity and immunogenicity •Potential transgene insertion into non-T cells •Unknown safety profile •Unknown durability |
| . | Pros . | Cons . |
|---|---|---|
| Accelerated cell manufacturing | •Reduced vein-to-vein time •Less resource intensive •Increased manufacturing capacity •Less differentiated T cells in final product •Potential for reduced T-cell doses | •Increased potential for contaminating tumor cells in product (particularly for hematological malignancies) •Potential for T cells having overly active phenotype, leading to increased toxicities •Complexity in product-release testing (e.g., inability to distinguish between transient protein expression from pseudo-transduction versus stable integration) |
| Process automation | •Reduced personnel and infrastructure costs •Reduced probability of human error •Potential for on-site manufacturing enabling fresh cell products | •Reduced capability to respond to patient-specific cell behaviors during manufacturing •Challenge in ensuring consistency across multiple sites for point-of-care manufacturing •Limited capacity to perform long-term release testing for fresh products |
| In vivo cell manufacturing | •Cost and time saving from eliminating need for ex vivo cell manufacturing •Potential for less differentiated T cells •Off-the shelf reagents instead of patient-specific products | •Potential genotoxicity and immunogenicity •Potential transgene insertion into non-T cells •Unknown safety profile •Unknown durability |