Hope for Cancer: Immune Checkpoint Drugs

The scientific fraternity reaffirmed their confidence in Immune Checkpoint Drugs by giving away Nobel Prize for Physiology and Medicine to Dr James P. Allison and Tasuku Honjo. These two are the scientists who found that if we block the immune checkpoint brakes it can pave way to cure cancer. Immune checkpoint proteins CTLA4 and PD1, and many more checkpoint proteins hold key to unlock cancer.

Drugs that inhibit these immune checkpoints – often made of antibodies –unleashes an immune system attack on cancer cells. Success has been found particularly in some patients with metastatic melanoma or Hodgkin lymphoma, and are showing promise in clinical trials involving patients with other types of cancer. They were used to treat AFL player Jarryd Roughead, businessman Ron Walker and former US president Jimmy Carter. Drugs pembrolizumab (Keytruda), ipilimumab (Yervoy), nivolumab (Opdivo), avelumab, durvalumab (Imfinzi) and atezolizumab are examples of  Immune Checkpoint Drugs.

image: Dr. James P Allison and Dr. Tasuku Honjo

Steps in the cancer-immunity cycle described  by Chen and Mellman

Step 1: Dead cancer cells release neoantigens that are captured by dendritic cells

Step 2: Dendritic cells process and present the major histocompatibility class I (MHCI) or major histocompatibility class II (MHCII)-bound neoantigen to T cells

Step 3: Effector T cells become primed and activated, including CD8+ cytotoxic T cells and CD4+ helper T cells that recognize the neoantigen/MHCI complex and neoantigen/MHCII complex, respectively

Step 4: Cytotoxic T cells travel to the tumor site

Step 5: Cytotoxic T cells infiltrate the tumor bed

Step 6: Cytotoxic T cells recognize cancer cells via the interaction between the antigen/MHCI complex and receptors

Step 7: Cytotoxic T cells destroy the cancer cells through signaling mechanisms. More neoantigens are released, which amplifies the T cell response in the next the cycle

The successful use of immune checkpoint inhibitors in recent years indeed brings some hope for cure and survival for those suffering from various cancers, but this treatment need extensive support from patient management team and nursing care. This is because of the side-effects that would be triggered off while taking this drug.  Specifically, immunotherapy can take some time before it start showing positive response compared to conventional chemotherapy. Patients may even experience stable disease or even progression after initial treatment. Also since this treatment would involve meddling with immune system, there are chances for flare up of overall immune reactions. This demands for constant monitoring and timely intervention. Patients need to be educated on these unique responses attributed to immunotherapy since they may be sometimes unexpected.