cancer immunotherapy

Introduction

The 4 FDA-approved cancer immunotherapies are checkpoint inhibitors

Epidemiology

• men tend to do better than women with cancer immunotherapy

Adverse effects

• checkpoint inhibitors may allow the immune system to attack intestines, liver, lungs, kidneys, adrenal, pituitary, heart, & the pancreas
• severe immune reactions in nearly 20% of patients, 50% if combination therapy used

Laboratory

• ploidy measurement or aneuploidy & chromosomal microdeletions may provide prognostic information regarding likelihood for success of cancer immunotherapy

Mechanism of action

• cancer cells can elude the immune system by engaging an immune checkpoint on a T-cell, effectively shuting down the T-cell
• checkpoint inhibitors, block that checkpoint & allow T-cells to attack the cancer cells
• TLR9 agonist CMP-001 restores response to checkpoint inhibitor pembrolizumab in 22% of patients with cutaneous melanoma

Comparative biology

• dual immunotherapy with intratumoral delivery of a TLR9 ligand with OX40 activation to ramp up T cell responses led to shrinkage of distant tumors & long-term survival of mice with breast cancer, colon cancer, melanoma & lymphoma
  • 87 of 90 mice were cured of cancer
  • in the remaining 3 mice, tumors again regressed after a 2nd treatment

Notes

• 2018 Nobel Prize in Physiology or Medicine 2018 awarded jointly to James P. Allison & Tasuku Honjo for their discovery of cancer therapy by inhibition of negative immune regulation

More general terms

• biotherapy (immunotherapy)

More specific terms

• adoptive cell transfer
• checkpoint inhibitor therapy
• chimeric antigen-receptor (CAR) T-cell therapy; tisagenlecleucel; CTL019 (Kymriah)
• oncolytic viral therapy

Additional terms

• checkpoint inhibitor; immune checkpoint inhibitor; PD-1/PD-L1 inhibitor