Table 1.
Preclinical CAR T cell approaches to improve trafficking.
| Reference | Tumor | TME | Appproach | Outcome(s) |
|---|---|---|---|---|
| [196] | B16 melanoma | Vasculature | VEFGR-2 CAR T cells in combination with anti-VEFG-A ligand antibody |
Combination of anti-VEFG-A ligand to overcome competition enhances CAR T cell activity |
| [197] | Murine breast carcinoma | ECM | Engineered macrophages to HER2 CAR T cells and production of metalloproteases as byproduct of activation | In addition to controlling HER2+ tumors, this approach decreased collagen deposition and facilitated T cell infiltration |
| [47] | Stroma-rich solid tumors | ECM | CAR T cells expressing enzyme heparanase (HPSE) | The expression of HPSE improves CAR T cell infiltration through degradation of the ECM |
| [198] | Breast, colon, melanoma, fibrosarcoma |
ECM | Fibroblast activated protein targeted CAR T cells (FAP-CAR T cells) | Toxicity and off-target effects in bone marrow killed mouse models and therapy showed limited antitumor results |
| [148] | Carcinomas | ECM | FAP-CAR T cells | Decreased tumor density and reduced autochthonous pancreatic cancer growth |
| [149] | Non-small cell lung carcinoma |
ECM | FAP-CAR T cells | Reduction in FAP positive stroma and improved antitumor killing alone or when paired with anti-EpHA2 CAR T cells |
| [199] | Hepatocellular carcinoma (HCC) |
Migration | CXCR2-expressing CAR T cells | Improved T cell migration and accumulation at the tumor site compared to control |
| [200] | Solid tumors | Hypoxemia | CD19 and B cell maturation antigen (BCMA) CAR T cells at normoxic and hypoxic oxygen levels | Hypoxic conditions attenuated CAR T cell expansion, differentiation to CD8 T cells, and cytokine production |
| [201] | Solid tumor | Hypoxemia | CAR T cells were transcriptionally paired to hypoxia response elements (HREs) including hypoxia-inducible-1 factor-alpha (HIF1α) | Hypoxia-induced CAR T cells showed improved antitumor activity in hypoxia compared with normoxia |
| [166] | Solid tumor | Immune cells | Delivery of developmental antigen-encoding RNA via nanoparticles | RNA loaded nanoparticles enhanced expansion and activity of CAR T cells in claudin-expression solid tumors |