Why can’t normal T cells kill leukaemia cells?

Why can’t normal T cells kill leukaemia cells?

Normal T cells have the ability to kill cancer cells but they must still be activated via binding to their target cell.

For activation to occur, two signals are required:

1. T cell receptor (TCR) binds antigen presented on MHC-I by the tumour cell.
2. co-stimulatory signal (not shown on diagram).

Cancer cells evade these activation mechanisms

CAR-T cells don't require MHC or co stimulation

CAR:

1. Directly recognises CD19 on B cells independent of MHC presentation
2. Contains integrated co-stimulatory domains

This allows CAR-T cells to overcome many of the limitations that prevent normal T cells from effectively eliminating cancer cells.

CAR-T cells don't require MHC or co stimulation

CAR:

1. Directly recognises CD19 on B cells independent of MHC presentation
2. Contains integrated co-stimulatory domains

This allows CAR-T cells to overcome many of the limitations that prevent normal T cells from effectively eliminating cancer cells.

Cancer cells: ↓ MHC molecules - cancer peptide is not presented to T cells so they can't be activated ↓ Co-stimulatory signals - T cells are not properly activated = Less T cell killing, cancer cells survive and continue proliferating