Checkpoint Inhibitors Boost Cancer Vaccine Research
Researchers are excited about the prospect to use vaccines in combination with checkpoint inhibitors to improve the body’s cancer-fighting ability.
Made up of irradiated tumor cells from patients with pancreatic cancers, the GVAX vaccine is then genetically modified with an immune booster, granulocyte-colony stimulating factor (GCSF). The idea is patients with these cancers may have shared antigens that the immune system can recognize . And, the advantage is that it's an off-the-shelf vaccine that does not need to be customized for each patient. With the recent addition of an immune checkpoint inhibitor, the early results appear to be even more encouraging, Dr Yarchoan said.
Investigators at Rutgers Cancer Institute in New Brunswick, New Jersey, also hope to develop an off-the-shelf vaccine. A 5-year clinical trial is expected to begin in the near future, testing a renamed poxvirus-based vaccine with nivolumab in patients with colorectal cancers that have metastasized to the liver. The experimental vaccine, now known as CV301, targets 2 tumor-associated antigens, which are overexpressed in multiple solid tumors, including colorectal cancers.6 “Checkpoint inhibitors are a big deal,” says Edmund Lattime, PhD, deputy director of the cancer institute, who is not surprised by the explosive interest in these agents or their synergy with vaccines. “But, it's important to realize checkpoint inhibitors were discovered not through cancer research, but through basic science research into how the immune system is regulated.”
Ultimately, Dr Lattime said, there is a far larger role for vaccines, which are generally less toxic than checkpoint inhibitors, as part of a pervasive strategy targeting different components of the immune system.
Dr Gulley agrees. A multifactorial approach that goes beyond combining checkpoint inhibitors with vaccines, he said, will be needed to be successful against the deadliest cancers. Not only must researchers first engage the immune system to recognize a tumor, they must expand the immune response and reduce the cancer's ability to suppress an immune response. Chemotherapy and radiation, too, will play a role, Dr Gulley said, in order to make the tumor easier to kill.
The National Cancer Institute, in fact, has just started a trial that includes patients with advanced prostate cancer and uses 4 experimental agents to target 5 different immunologic pathways.7 Besides using a vaccine that targets a transcription factor involved in metastasis, Dr Gulley explained, investigators will use IL15 as an immune booster, an anti-PD1 checkpoint inhibitor, and an enzyme that inhibits regulatory T-cell function in tumors' microenvironment.
“Potentially, we've seen with some immune-based therapies, cases where tumors have gone away and you don't need additional therapy,” he said. “If we could turn cancer into a chronic disease, that would be great — and curing it, obviously, [would be] even better.”
Schlom J, Gulley JL. Vaccines as an integral component of cancer immunotherapy. JAMA.2018;320:2195-2196.
- Cheever MA, Higano CS. PROVENGE (sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clin Cancer Research. 2011;17:3250-3526.
- FDA approves Yervoy (Ipilimumab) for the treatment of patients with newly diagnosed or previously unresectable or metastatic melanoma, the deadliest from of skin cancer [news release]. Princeton, NJ: Bristol-Myers Squibb; March 25, 2011. Accessed January 10, 2019.
- Garlapow M. Immune Checkpoint Inhibitors: A Review of Side Effects, Their Causes and Incidence. Oncology Nurse Advisor website. Published September 25, 2018. Accessed February 1, 2018.
- Turning the immune system on pancreatic cancer. Johns Hopkins Medicine website. Published April 2, 2018. Accessed February 1, 2019.
- Exploring a new treatment for metastatic colorectal cancer. Rutgers Cancer Institute of New Jersey website. Published June 19, 2018. Accessed January 10, 2019.
- Redman J, Steinberg S, Gulley J. Quick efficacy seeking trial (QuEST1): a novel combination immunotherapy study designed for rapid clinical signal assessment metastatic castration-resistant prostate cancer. J Immunother Cancer. 2018;6(1):91.