Therapeutic Application of Immune Checkpoints in Cancer

Cancer immunotherapy

Cancer immunotherapy is a new developed therapy used to treat cancer patients involving components of immune system. This can be done through two methods, stimulating immune system of patient to work harder to attack cancer cells and giving immune system components of patients like immune system proteins, respectively.

According to target types, there are five approaches in cancer immunotherapy.

• Tumor vaccine targeting tumor antigen and antigen presenting cell
• Cytokine therapy targeting antigen presenting cell and T, B cell
• Cell therapy targeting antigen presenting cell and T, B cell
• Immune checkpoint inhibition target T cell
• Tumor micro-environment regulation targeting cancer cells

Figure 1. cancer immunotherapy.

Biologic rationale for immune checkpoint inhibition as cancer therapy

Along with the rapidly development of cancer immunotherapy, immune checkpoint inhibitors have attracted a lot of attention in recent years. cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays a vital role in attenuating the activation of naïve as well as memory T cells through interaction with its ligands B7-1/CD80 and B7-2/CD86. Different with CTLA-4, programmed cell death protein 1 (PD-1) is primarily involved in adjusting T cell activity in peripheral tissues through engagement with PD-L1 and PD-L2. The discovery of these inhibitory immune checkpoints is essential for the development of immune checkpoint inhibitors, aiming to remove coinhibitory signals blocking anti-cancer T cell responses.

Figure 2. Blockade of CTLA-4 and PD-1 in tumor immunotherapy.

Immune checkpoint inhibitors improve patient survival

During recent years, FDA has already approved several immune checkpoint inhibitors including PD-1 and CTLA-4 inhibitors.

Figure 3. Immune checkpoint inhibitors improve patient survival. Ipilimumab is FDA approved inhibitor of CTLA-4.

Reference

1. Antoni Ribas(2012). Tumor Immunotherapy Directed at PD-1. NEJM. 366:2517.