Advantages and disadvantages of different sources to produce T cells for immunotherapy
| Source . | Advantages . | Disadvantages . |
|---|---|---|
| Donor peripheral blood | Healthy donors have abundant T cell populations, and genetic engineering and expansion can be performed. Donors with high T cell yields can provide treatment doses for multiple patients. | Careful matching of the donors and recipients is required to avoid GVHD or allo-rejection. 100% purity of genetic engineering required to avoid GVHD or allo-rejection is a challenge. |
| Autologous peripheral blood | Autologous peripheral blood CAR T cell therapy is the gold standard in the field. This approach can lead to long, durable remissions in some patients with B-cell malignancies. | Potential for serious side effects. Complex manufacturing with considerable lag time. Reliant on the quality of patient T cells, which can be poor due to disease and previous treatments. Very high cost. |
| Cord blood T cells | T cells in cord blood are more naïve than those in peripheral blood and could theoretically, exhibit less exhaustion and better persistence after adoptive transfer compared to T cells derived from peripheral blood. | New engineering strategies would be needed to eliminate the potential for GVHD. Few groups have tested this approach and studies have been done in vitro and using immunodeficient mice. |
| iPSCs | All the advantages listed in Table 2 plus disruption of the TRAC locus at the iPSC stage can abolish TCRα chain expression, allowing for the generation of CAR T cells without TCR-driven GVHD. | Labor-intensive manufacturing process requires genetic engineering and cell culture expertise. Clinical testing is still in early stages. |
| Source . | Advantages . | Disadvantages . |
|---|---|---|
| Donor peripheral blood | Healthy donors have abundant T cell populations, and genetic engineering and expansion can be performed. Donors with high T cell yields can provide treatment doses for multiple patients. | Careful matching of the donors and recipients is required to avoid GVHD or allo-rejection. 100% purity of genetic engineering required to avoid GVHD or allo-rejection is a challenge. |
| Autologous peripheral blood | Autologous peripheral blood CAR T cell therapy is the gold standard in the field. This approach can lead to long, durable remissions in some patients with B-cell malignancies. | Potential for serious side effects. Complex manufacturing with considerable lag time. Reliant on the quality of patient T cells, which can be poor due to disease and previous treatments. Very high cost. |
| Cord blood T cells | T cells in cord blood are more naïve than those in peripheral blood and could theoretically, exhibit less exhaustion and better persistence after adoptive transfer compared to T cells derived from peripheral blood. | New engineering strategies would be needed to eliminate the potential for GVHD. Few groups have tested this approach and studies have been done in vitro and using immunodeficient mice. |
| iPSCs | All the advantages listed in Table 2 plus disruption of the TRAC locus at the iPSC stage can abolish TCRα chain expression, allowing for the generation of CAR T cells without TCR-driven GVHD. | Labor-intensive manufacturing process requires genetic engineering and cell culture expertise. Clinical testing is still in early stages. |
GVHD, graft-versus-host-disease.