SPOTLIGHT On the Horizon for Immunotherapy As highlighted throughout this section, cancer immunotherapy has revolutionized cancer treatment and brought hope to countless patients with cancer who otherwise have no or limited treatment options. Thanks to research, progress in the field of immunotherapy is continuing at an unprecedented pace. Researchers are exploring several exciting new avenues to increase the number of cancer types that are treatable with immunotherapy, some of which are outlined in this section. A New Era of mRNAbased Cancer Vaccines Cancer vaccines work by boosting the magnitude of a patient’s T cells with natural cancer-killing capacity. They do this by providing large amounts of the small pieces of cancer-specific proteins that T cells need to recognize on the surface of tumor cells in order to eliminate the cancer cells (515). Although the concept of cancer vaccines is not new, developing effective cancer vaccines has been challenging, as evidenced by the fact that, as of July 31, 2023, there is only one FDA approved therapeutic cancer vaccine (516). The success of mRNA-based vaccines against SARS-CoV-2— the virus that caused the COVID-19 pandemic—has renewed interest in using mRNA-based vaccines to treat cancer (517). Furthermore, exciting new technological advances in sequencing DNA, RNA, and proteins are helping to catalogue abnormal proteins present in tumor cells that represent potential targets. Researchers are leveraging this knowledge to develop mRNA-based cancer vaccines that are tumor and patient specific. The enormous potential of cancer vaccines is underscored by the findings of a recent study in pancreatic cancer, a particularly aggressive disease (518). Researchers developed an mRNAbased cancer vaccine that was tailored toward the abnormalities in the tumors in each of the 16 patients with pancreatic cancer who participated in the study. The vaccine stimulated an immune response against the cancer in half of the patients, and those who responded to the treatment did not have signs of cancer at the 18-months follow-up. These findings are extremely promising because pancreatic cancer has very low survival rate and very few treatment options (518). Another recent study evaluated the effectiveness of an mRNA-based vaccine for the treatment of metastatic melanoma. The results showed that the combination of the vaccine and the ICI pembrolizumab reduced the likelihood of cancer recurrence or death by nearly 44 percent compared to pembrolizumab treatment alone, which is a current standard of care for these patients (519). Cancer cells change constantly as cancer progresses (see Understanding the Path to Cancer Development, p. 24). As a result, the types of alterations in tumor proteins, as well as protein fragments present on the surface of tumor cells, also change. Advantages of mRNA-based cancer vaccines are that these therapeutics can induce responses to multiple targets, thus addressing heterogeneity, can be tailored against a patient’s changing tumor, and can be produced rapidly (520). This latter capability allows researchers to periodically monitor which protein pieces are present on the surface of tumor cells of a patient, and to develop new versions of the vaccines that are more effective. Therapeutic mRNA-based cancer vaccines have not yet been FDA approved for cancer treatment. However, a recent review of the early clinical studies evaluating the potential of mRNA-based vaccines in treating various types of cancer shows that findings from many of these ongoing studies are encouraging (521), and point to exciting new developments in this area of cancer medicine. A New Generation of Immune Checkpoint Inhibitors As discussed earlier, ICIs are one of the most widely effective cancer immunotherapies. As of July 31, 2023, FDA has approved 11 ICIs for the treatment of 20 cancer types (see Figure 20, p. 127). Although ICI treatment can lead to better long-term outcomes compared to other anticancer agents for certain patients, most patients do not respond to ICIs, and many who do respond at first eventually develop resistance to the treatment (522). MHC-PEPTIDE PRESENTATION IN NORMAL CELLS VS TUMOR CELLS Normal cell surface antigen Cancer-associated antigen Normal cell Cancer cell Researchers have developed an artificial intelligencebased tool, which uses the knowledge that blood vessels around tumors are often abnormal and predicts the likelihood with which the tumor will respond to ICI treatment (523). AI AACR Cancer Progress Report 2023 Immunotherapy: Pushing the Frontier of Cancer Medicine 128
RkJQdWJsaXNoZXIy NTkzMzk=