CAR T Cell therapy: Teaching patients’ immune cells to fight their cancers

Chimeric antigen receptor (CAR) T cells are types of white blood cells (T cells) harboring synthetic receptors that, upon recognition and attachment to a specific molecule on tumor cells, drive an immune response that culminates with the death of the malignant cells.

The first-generation CAR molecule was engineered by Prof. Zelig Eshhar and colleagues at the Weizmann Institute Of Science (Israel).

The main challenges posed to CAR T cell therapy by solid tumors can be described in two steps: identifying and attacking the tumor

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.

CAR T success in treating solid tumors is quite limited

  • 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.

On-target/off-tumor toxicity precludes the use of CAR T therapy in the treatment of solid cancers