In order for the first generation immunotherapy checkpoint blockade drugs to work, they require that there be properly trained and armed killer immune cells resident in the tumor beds. However, it is rare for cancer patients to have killer cells infiltrating tumor sites. Accordingly, one aim of research for second generation immunotherapy drugs is to elicit the formation of killer immune cells in patients where these cells don’t exist and combine this technology with checkpoint blockade. In order to elicit killer cells which are able to kill tumor cells, researchers are working to develop cancer vaccines. Another approach is to genetically engineer a patient’s killer cells outside the body so that they will recognize tumor cells and then infuse these engineered cells back to the same patient. A popular technology for this approach is known as “CAR-T” cells.

Another problem limiting the effectiveness of first generation checkpoint blockade drugs is that these drugs block only one checkpoint signal that occurs at the end of the immune cascade. However, tumors have been found to express numerous types of negative checkpoint signals and there are various other checkpoints that occur along the immune cascade leading to development of killer cells. Accordingly, another approach for development of second generation immunotherapy drugs is to develop checkpoint blockade drug cocktails that can block numerous unwanted signals to immune cells.

The problem with these approaches is that they are not economically feasible. Just one checkpoint drug now costs over US$100,000. The only FDA approved cancer vaccine, Provenge (Sipuleucel-T), costs over US$90,000 for a course of treatment. Accordingly, the costs of combining multiple checkpoint blockade drugs or combining checkpoint blockade with cancer vaccines is a solution that may not be economically feasible.