Cancer immunotherapy—which harnesses the immune system to combat cancer—has revolutionized oncology drug development in the past 5 years. By modulating various components of the immune system, researchers have been able to develop highly promising new treatments for several cancers, including melanoma, non-small-cell lung cancer, renal cell carcinoma and Hodgkin lymphoma. A key approach that has proved particularly successful so far is the inhibition of immune checkpoint proteins that regulate the activity of T cells, thereby ‘releasing the brakes’ from T cells to enable them to attack cancer cells (Fig. 1a). Cytotoxic T lymphocyte-associated antigen 4 (CTLA4), programmed cell death protein 1 (PD1) and programmed cell death 1 ligand 1 (PDL1) are three checkpoint proteins that inhibitors have been successfully developed for (Fig. 1b).
The first checkpoint inhibitor to reach the market was Yervoy (ipilimumab), developed by Bristol-Myers Squibb, which was approved in March 2011 for unresectable or metastatic melanoma. Since then, three further checkpoint inhibitors—the PD1 inhibitors Opdivo (nivolumab) and Keytruda (pembrolizumab), and the PDL1 inhibitor Tecentriq (atezolizumab)—have been approved for various cancers. Given the huge impact of this first wave of checkpoint inhibitors, companies are now exploring the potential of combining checkpoint inhibitors with each other and with other cancer immunotherapies, as well as with drugs in different classes such as epigenetic modulators and kinase inhibitors. This has led to a flurry of deal activity involving many major pharma companies as each tries to establish its place in the rapidly growing cancer immunotherapies market.(Fig. 2) (March 2016 BioPharma Dealmakers, pB2).
Figure 2: A timeline of selected approvals and collaborations for checkpoint inhibitors. BMS, Bristol-Myers Squibb; CAR, chimeric antigen receptor; FDA, US Food and Drug Administration; GSK, GlaxoSmithKline; mAb, monoclonal antibody; nab, nanoparticle-albumin-bound; NHL, non-Hodgkin lymphoma; HL, Hodgkin lymphoma; HNSCC, head and neck squamous cell carcinoma; NSCLC, non-small-cell lung cancer; RCC, renal cell carcinoma. *Known as MSD outside the United States and Canada.
