Despite the outstanding results achieved for hematological malignancies (high remission rates obtained with CD19-CAR T cells), no encouraging data have been published for solid tumors. The limited success of the CAR T therapy in solid tumors is mostly a result of two factors:
- The “hostile” tumor microenvironment that comprises physical barriers, immune checkpoints, alterations in the tumor metabolic environment and immunosuppressive signals.
- The “on-target/off-tumor toxicity” caused by target antigen expression on normal cells which results in CAR T-mediated killing of healthy tissue. This undesirable effect has caused severe events with fatal outcomes.
- Lack of tumor-specific targets reduces current development to a narrow niche such as hematological cancers
- Target proteins overexpressed in tumors are often expressed in normal cells, resulting in safety concerns