Immunotherapy in Cancer

Evading immune destruction was described as an emerging hallmark of cancer in 2011 (Hanahan and Weinberg 2011). Immunotherapy in cancer refers to several different approaches that involve immune system activation. These therapeutic approaches include the use of cytokines, cancer vaccines, cellular therapy, and immune checkpoint inhibitors to modulate immune responses against tumors, or to break down the tumor’s defense mechanisms against immune responses.

Immune checkpoint inhibitors target several pathways related to T-cell activation, proliferation, and induction of tumor cell death. The specific targets of the immune checkpoint inhibitors are expressed on the cell surface of the tumor-specific T cell, the tumor cell, or the antigen-presenting cell including cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death-1 (PD-1), and programmed cell death ligand-1 (PD-L1; Drake et al. 2014). Immune checkpoint inhibitors are an active area of investigation with new classes of anti-CTLA-4, anti-PD-1, and anti-PD-L1 monoclonal antibodies in different stages of development. The CTLA-4 inhibitor ipilimumab was the first and only agent in this class to receive FDA approval (FDA 2011). Pembrolizumab was the first PD-1 inhibitor to receive FDA approval and nivolumab was approved later in 2014 (FDA 2014). The first PD-L1 inhibitor to receive FDA approval was atezolizumab in 2016 and durvalumab and avelumab were both approved in 2017 (FDA 2016, FDA 2017).

Here, we present data on the use of immune checkpoint inhibitors in melanoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma (HCC), urothelial cancer, bladder cancer, and head and neck cancer. However, these agents have demonstrated activity in multiple other tumor types to date, including gastric cancer and others. We will continue to update this website to incorporate other tumor types.


Drug class Target Agent Diseases with trial results reported
CTLA-4 inhibitors CTLA-4 ipilimumab (Yervoy) melanoma
non-small cell lung cancer
small cell lung cancer
renal cell carcinoma
tremelimumab melanoma
PD-1 inhibitors PD-1 nivolumab (Opdivo) Hodgkin lymphoma
melanoma
non-small cell lung cancer
small cell lung cancer
hepatocellular carcinoma
renal cell carcinoma
ovarian cancer
head and neck cancer
urothelial cancer
colorectal cancer (MSI-H/dMMR)
pembrolizumab (Keytruda) melanoma
non-small cell lung cancer
small cell lung cancer
head and neck cancer
urothelial cancer
triple negative breast cancer
mesothelioma
Hodgkin lymphoma
gastric cancer
solid tumors (MSI-H/dMMR)
colorectal cancer (MSI-H/dMMR)
PD-L1 inhibitors PD-L1
durvalumab (Imfinzi) urothelial cancer
head and neck cancer
non-small cell lung cancer
atezolizumab (Tecentriq) urothelial cancer
melanoma
non-small cell lung cancer
renal cell carcinoma
triple negative breast cancer
avelumab (Bavencio) Merkel cell carcinoma
urothelial cancer

 

Contributors: Wade T. Iams, M.D., Douglas Johnson, M.D., Christine M. Lovly, M.D., Ph.D.

Suggested Citation: Iams, W., D. Johnson, C. Lovly. 2018. Immunotherapy in Cancer. My Cancer Genome https://www.padiracinnovation.org/content/molecular-medicine/immunotherapy-in-cancer/ (Updated May 25).

Last Updated: May 25, 2018

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