What is the mechanism of action of immune checkpoint inhibitors?

Immunotherapy drugs called immune checkpoint inhibitors work by blocking checkpoint proteins from binding with their partner proteins. This prevents the “off” signal from being sent, allowing the T cells to kill cancer cells. One such drug acts against a checkpoint protein called CTLA-4.

What is the mechanism of action of Nivolumab?

Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response, resulting in decreased tumor growth.

How was immunotherapy Discovered?

The earliest case of cancer immunotherapy can be traced back to 1891, when William Coley, the father of immunotherapy, first attempted to leverage the immune system to treat cancer after noticing that mixtures of live and inactivated Streptococcus pyogenes and Serratia marcescens could cause tumor regression in sarcoma …

How does CTLA-4 Blockade work?

It is thought that the blockade of CTLA-4 most likely impacts the stage of T cell activation in the draining lymph nodes when CTLA-4 expressing Tregs remove CD80/CD86 from the surface of antigen-presenting cells, thereby reducing their ability to effectively stimulate tumor-specific T cells (24).

Do immune checkpoint inhibitors target lymphocyte receptors?

Immune checkpoint inhibitors target lymphocytes rather than cancer cells, and evoke an anti-tumor immune reaction.

What is a checkpoint inhibitor drug?

Checkpoint inhibitors are a type of immunotherapy. They are a treatment for cancers such as melanoma skin cancer and lung cancer. These drugs block different checkpoint proteins. You might also hear them named after these checkpoint proteins – for example, CTLA-4 inhibitors, PD-1 inhibitors and PD-L1 inhibitors.

What are checkpoint inhibitor drugs?

Is Nivolumab a checkpoint inhibitor?

Nivolumab, a fully human immunoglobulin G4 PD-1 immune checkpoint inhibitor antibody, blocks PD-1 and promotes antitumor immunity, and it is effective for treating non-small-cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC) and other cancers.

Who introduced immunotherapy?

The next significant advances came from William Bradley Coley who is known today as the Father of Immunotherapy. Coley first attempted to harness the immune system for treating bone cancer in 1891 (6, 7).

When did they discover immunotherapy?

The idea of using immunotherapy in cancer, in general, returned to prominence when Thomas and Burnet first proposed the theory of cancer immunosurveillance in 1957. They suggested that lymphocytes acted as sentinels to identify and eliminate somatic cells transformed by spontaneous mutations.

Is CTLA-4 a checkpoint inhibitor?

CTLA-4 is considered the “leader” of the immune checkpoint inhibitors, as it stops potentially autoreactive T cells at the initial stage of naive T-cell activation, typically in lymph nodes.

How does the CTA 4 antibody work?

CTLA-4, expressed exclusively on T-cells, acts as a negative co-stimulatory signal, inhibiting T-cell activation and proliferation to maintain self-tolerance and protect from autoimmunity [4].