With each new conference on cancer comes even more reasons to believe in the promise of immunotherapy—and ASCO17 was no different. (If you haven’t already, you can read our daily highlights here: Day 1, Day 2, Day 3, and Days 4 & 5.) The presentations at the conference can be grouped into seven distinct areas of exploration and progress, and this final recap of this year’s meeting seeks to put these in context and explain what they mean for cancer patients.
- Improved Biomarkers
Immunotherapies don’t work for every patient yet, and even when they do there can be side effects. Therefore, it would be immensely helpful for doctors to be able to tell which patients are most likely to benefit from immunotherapy as well as whether or not the treatment is working. This can help ensure that immunotherapy is given at just the right times to just the right patients. To accomplish this, doctors have sought to use biological signals called biomarkers, and ASCO17 revealed several that appear to have useful clinical applications. These include a tumor’s genomic stability, circulating tumor DNA, microRNAs in saliva, immune cell infiltration into tumors, germline mutations, and even the presence of certain bacterial species. An online tool was unveiled that can help doctors deal with side effects that do occur during treatment.
- Immunotherapy as an Earlier Option
Currently, most immunotherapies are only approved for patients with advanced cancer that has already spread to other organs and against which no other options are effective. Hot on the heels of pembrolizumab’s first-line approval for advanced lung cancer, ASCO17 showed that immunotherapies can also be effective as first-line treatments against several other types of advanced cancers. Furthermore, it was also revealed that patients with early-stage cancer can benefit from immunotherapy, either before or after surgery, too.
- Targeting New Immune Molecules
For the past several years, PD-1 and PD-L1 checkpoints have dominated immunotherapy approaches. Now, ASCO17 revealed that newer and more diverse immune-based targets are beginning to show promise in the clinic, and may allow even more patients to benefit from immunotherapy. These new targets include IDO1, LAG-3, GITR, TLRs, CSF1R, CD27, DRD2, OX40, arginase, and A2AR, among others.
- Expanding Cell-Based Applications
Cell-based immunotherapies, especially CAR (chimeric antigen receptor) T cells, have been very effective in patients with blood cancers such as leukemia and lymphoma. At ASCO17, newer versions of these CARs that employ alternative stimulatory mechanisms were highlighted, along with cell-based immunotherapies with the potential to treat patients with a much wider range of cancers, including liver cancer, lung cancer, ovarian cancer, pancreatic cancer, and sarcoma. These relied on targeting tumor-specific proteins, such as mesothelin, GCP3, BCMA, and NY-ESO-1, that hadn’t yet been exploited as successfully using traditional cell-based therapies.
- Customized Antibodies
Antibodies have traditionally been one of the more effectively utilized immunotherapies, and ASCO17 highlighted the effectiveness of both traditional antibodies as well as those that have been engineered with customized properties for several cancer types. With respect to the customized antibodies, the two main approaches were antibody-drug conjugates (ADCs), which have toxic anti-tumor drugs attached to tumor-targeting antibodies, and bi-specific antibodies, which can target two distinct molecules at the same time and make it even easier for the immune system to interact with and eliminate tumor cells.
- Vaccines & Viruses
As of now, there are a total of three FDA-approved immunotherapies involving vaccines and/or oncolytic viruses, but at ASCO17 scientists highlighted several other promising applications of these approaches. With respect to viruses, promising results were achieved with adenoviruses, a reovirus, and a coxsackievirus. With respect to vaccines, promising results were achieved using a personalized peptide-based approach, an antibody-based approach, a combination approach employing two complementary immune-boosting agents, and one approach that utilized patients’ own modified tumor cells.
Again, while PD-1/PD-L1 checkpoint immunotherapies have dominated the landscape recently, they are still only effective for a subset of patients, especially those whose tumors are “hot”—that is, tumors that the immune system has already recognized and mounted an initial response against. Doctors have long theorized that combining different approaches could perhaps help turn non-responsive, “cold” tumors into hot ones that respond to immunotherapy, and were waiting for the data to back up the idea. At ASCO17, many of these ideas showed preliminary signs of promise, including one checkpoint immunotherapy combination evaluated in a clinical trial that was sponsored and organized by the Cancer Research Institute’s Clinical Accelerator.
This concludes our coverage of ASCO17. Be sure to follow our blog for future updates from the field of cancer immunotherapy!