An experimental cancer vaccine, currently in early-stage development at the University of California San Francisco (UCSF), may someday be an alternative for patients with acute myeloid leukemia (AML) who relapse or are unable to tolerate existing intensive treatments.
“Cancer vaccines have been in use for some time, both as a preventative measure (HPV, hepatitis B), as well as a therapeutic [measure] where the vaccine is composed of antigens that can educate the immune system to ward off disease,” wrote Ross Okamura, PhD, senior science officer at the California Institute of Regenerative Medicine, in an article about the research. However, “identifying an antigen to specifically target AML curatively has been difficult,” he noted.
Although many immunotherapies for AML have been explored, none have ever been shown to reduced relapse rates. By engineering cancer cells into a personalized vaccine tested on models of AML, researchers at UCSF’s Helen Diller Family Comprehensive Cancer Center were able to trigger a leukemia-specific immune response that overcame disease-related and age-related factors that would otherwise allow residual AML cells to persist after chemotherapy.
Study investigator Karin Gaensler, MD, who is a professor in the Department of Medicine (Hematology/Oncology) and the Krishnamurthi Endowed Chair in Hematological Malignancies at UCSF, noted in the UCSF article that the personalized vaccine in development is designed to stimulate graft versus leukemia-like effects in transplant-ineligible patients.
The UCSF team utilizes a two-pronged strategy to boost the immune system. First, they extract patient AML cells and then modify them to express the protein CD80, which is absent on AML cells. Next, they modify the patient’s leukemia cells to produce an immune stimulatory protein, interleukin-15 (IL-15), in combination with its receptor.
As a next step, the UCSF team is now working on developing the manufacturing process for the lentiviral vector, the method used to engineer cancer cells. In addition, one of the UCSF team’s collaborators, Farzin Farzaneh, PhD, of Kings College London, helped develop a different AML vaccine product and has obtained clinical trial approvals in Europe.
Farzaneh et al initiated a phase I trial in which lentiviral vectors are used to genetically modify AML cells to express CD80 and IL-2. By combining allogeneic hematopoietic stem cell transplantation (HSCT) with immunization, and by using the autologous AML cells expressing CD80 and IL-2, the team hopes to stimulate immune-mediated eradication of residual AML cells.
Gaensler said that significant advances are now occurring thanks to the unique collaboration between diverse investigators around the world who are pursuing various novel immune therapies. She and her team envision developing a vaccine in which an older patient’s AML cells are collected at diagnosis. If the initial chemotherapy is successful and the patient achieves remission, he or she would be vaccinated using his or her own engineered cells.
Mark James Levis, MD, PhD, program leader of the Hematologic Malignancies and Bone Marrow Transplant Program at Sidney Kimmel Comprehensive Cancer Center and a professor of Oncology at Johns Hopkins Medicine in Baltimore, told Cancer Network that these vaccine approaches sound very promising.
However, he said, there is a concern that patients may have unrealistic expectations if they are not fully aware of how much more research is required before such vaccines become available in the clinic. “Patients should not be given false hope about this,” Levis said. “It has always been the case in this field.”