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Immunotherapy

The human immune system has innate system and adaptive system

  • Innate system – eg macrophages, neutrophils – broad spectrum response without memory
  • Adaptive system – T cells and B cells – receptors which recognise specific antigens/anti-presenting cells – immunological memory with enhanced response

 

Interaction between innate and adaptive systems vital for generating competent immune response.

The immune system has a few roles in preventing cancer:

  1. Eliminating viruses which are carcinogenic
  2. Resolving acute inflammation and preventing chronic inflammation which can be carcinogenic
  3. Identifying and eliminating transformed/malignant cells

 

Immunotherapy aims to harness these properties to treat cancer.

There are two main immunotherapy strategies:

  1. Therapeutic vaccination
    1. g. BCG uses attenuated M.bovis to induce an immune response which attacks abnormal urothelium and tumour
  2. Targeting immune checkpoints

 

Immune checkpoint inhibition

Immune checkpoints are regulators of the immune system which allow self-tolerance – preventing unwanted attacks.

Checkpoint inhibitors exploit these pathways by downregulating these checkpoints and allowing the immune cells to enhance their response – “taking off the brakes”.

The pathways exploited are ligand/receptor interactions between antigen presenting cells, T cells and tumour cells.

 

Cytotoxic T-lymphocyte associated protein-4 (CTLA-4) is on the surface of T-cells and downregulates anti-tumour cell action.

  • Monoclonal antibodies block CTLA-4 and therefore stop the down-regulation, enhancing the anti-tumour activity of T cells
  • e.g. ipilimumab

 

Programmed cell death-1 (PD-1) protein/receptor and its ligand (PDL-1)

PD-1 receptor is on T cells – in normal settings, with PD-1 activated, the T-cell is made to be inactive.

  • Monoclonal antibodies to PD-1 or PDL-1 block it, allow the T-cell to remain active continuously, enhancing anti-tumour activity
  • e.g. pembrolizumab, nivolumab

 

Side effects of immunotherapy

  • Rash 30 %
  • Hypothyroidism 20 %
  • Colitis
  • Hepatitis
  • Encephalitis
  • Nephritis
  • Pneumonitis
  • Hypoadrenalism
  • Diabetes
  • “Unusual immune mediated side effects”