Immunotherapy in Drug Discovery & Development

Immunotherapy is a type of cancer treatment that uses the body's immune system to fight diseases such as cancer. The method can boost or alter the immune system's work to find and attack cancer cells. Several types of immunotherapies are used to treat cancer, including immune checkpoint inhibitors, T-cell transfer therapy, monoclonal antibodies, treatment vaccines, and oncolytic virus. Different types of immunotherapy work in different ways and they can be used alone or combined with other cancer treatments. Some reports show that the combination of multiple tumor immunotherapy may be an effective strategy for treating cancer.

Fig.1 Cancer immunotherapy approaches are classified into passive and active (Papaioannou, 2016).

Immune Checkpoint Inhibitors

Immune checkpoint inhibitors are drugs that block immune checkpoints to allow immune cells to respond more strongly to cancer. These checkpoints are a normal part of the immune system and naturally, stop the immune system’s response and prevent it from attacking healthy cells. The cancer cells can utilize them to hide from the immune system. The common checkpoints are the PD-1/PD-L1 and CTLA-4 pathways.

Targeted Monoclonal Antibodies

Monoclonal antibodies are man-made versions of immune system proteins to boost your body’s natural antibodies or act as antibodies themselves. The monoclonal antibodies can be designed to bind to specific targets on cancer cells. They can be used to block the activity of abnormal proteins in cancer cells and target specific genes, proteins, or tissue environments that help tumors grow and survive.

Cancer Vaccines

Cancer vaccines are a type of substance put into the body to start an immune response against certain diseases. The common cancer vaccines are cancer prevention vaccines and cancer treatment vaccines. The former is designed for healthy people to help prevent infections. The latter is for treating cancer and is used in people who already have cancer. The treatment vaccines can help the immune system recognize the antigens and destroy cancer cells.

Adoptive Cell Therapies

Adoptive cell therapy (ACT) is a kind of immunotherapy, involving the autologous or allogeneic transplant of tumor-infiltrating lymphocyte (TIL) and genetically engineered T cells expressing novel T cell receptors (TCR) or chimeric antigen receptors (CAR). The ACT aims at infusing immune cells with direct anti-tumor activity and these treatments have shown promising results in various tumor types. The use of CD19-directed CAR T cell therapy has achieved the most successful results in hematological malignancies and has been approved by the FDA.

Fig.2 Adoptive cell therapy paradigm illustrating major dillemas (Cohen, 2017).

Oncolytic Virus Therapies

Oncolytic virus therapy is a treatment of using a virus that infects and lyses cancer cells but not normal cells, which is perhaps the next breakthrough in cancer treatment following the success in immunotherapy. Oncolytic viruses can be further modified to enhance the antitumor immunity and the ability to target cancer cells. Today, adenoviruses, measles viruses, herpes simplex virus, vesicular stomatitis virus, and vaccinia virus are under preclinical and clinical development for cancer therapy.

References

1. Papaioannou, N., Beniata, O., Vitsos, P., Tsitsilonis, O. and Samara, P., 2016. Harnessing the immune system to improve cancer therapy. Annals of Translational Medicine, 4(14), pp.261-261.
2. Cohen, J., Merims, S., Frank, S., Engelstein, R., Peretz, T. and Lotem, M., 2017. Adoptive cell therapy: past, present and future. Immunotherapy, 9(2), pp.183-196.