Chapter 89
Cancer — 16
Checkpoint inhibitors and antibody-conjugate drugs are only a couple of the enhancements that are ramping up our immune response against cancer. Modified oncolytic viruses can infect the tumor, changing it immunologically from “cold” to “hot,” activating inflammatory responses, with or without a checkpoint inhibitor. While they had a checkered track record for success, recent reports in bladder cancer and other refractory tumors are promising.
Not only are there antibody-drug conjugates but also cell-drug conjugates. Chemotherapy or immunotherapy drugs, such as interleukin-15 or interleukin-2, can be attached to T cells, red cells, and platelets on clinical trials of various cancers.
It has become clear that our current cancer immunotherapy approaches are helping but are all too often insufficient to achieve durable success. The addition of Janus kinase inhibitors (JAKs) combined with checkpoint inhibitors led to increased success against refractory Hodgkin lymphoma and non–small cell lung cancer. The mechanism of benefit, “JAK-ing” up the immune response, appears to be blocking the immunosuppressive effect of interferons secreted by T cells, restoring their ability to kill cancer cells.
We know the gut microbiome constituents have a substantial influence on the success of cancer immunotherapy, but it is not assessed in patients with cancer, no less ways to modulate it with prebiotics, probiotics, or bacterial consortia (introduction of many strains). Clinical trials are underway to test such interventions.
Two platforms that further leverage our immune system—vaccines and engineered cells—are concurrently emerging, substantially building on the early success of immunotherapy. Cancer vaccines in the form of DNA, mRNA, or peptides, packaged in nanoparticles, cells, or naked, are being used to induce a higher-grade immune response. Using repeat shots, the goal is to train a person’s immune system to recognize tumor cells and destroy them. The vaccines are made against proteins on the cancer cell surface known as neoantigens or target commonly mutated variants of driver genes such as KRAS or TP53. The “vaccine on demand” process for making these customized vaccines is interesting, as described by Elizabeth Sullivan, head of operations for the personalized vaccines program at Moderna: