For today’s sufferers of the blood cancer acute myeloid leukemia (AML), standard chemotherapy remains the most common course of treatment, but the risk of recurrence is high and occurs in almost half of patients. In search of therapies that can offer longer-term protection, scientists at Harvard University have developed a new type of vaccine that when combined with chemotherapy proved highly effective in mice, eliminating the cancer cells and stopping them from coming back for some time after.
The vaccine works much like all vaccines do, in the sense that it trains the body’s immune system to identify a risk (in this case cancerous cells), and propels it into action. Where most cancer vaccines under development are liquid and made to tackle solid tumors, the scientists at Harvard’s Wyss Institute instead put together a solid vaccine to take out a liquid foe.
“We have previously developed cancer vaccines against solid tumors, and we were curious to see if this technology would also be effective at treating a blood cancer like AML,” says co-first author Nisarg Shah. “The promising outcomes of the combination of this vaccine with chemotherapy may translate to human vaccines that can be personalized yet offer off-the-shelf convenience.”
Consisting of biomaterials built onto a disk-shaped “cryogel” scaffold, the vaccine is loaded with biomolecules and antigens specific to AML cancer cells to stir up an immune response in their presence. The hope was that the therapy would not only swiftly recognize and destroy the AML cells, but remain vigilant in fending off any future attacks over the longer term.
The team first put the vaccine to the test in healthy mice, and watched on as it brought about a strong immune response through the activation of a large number of T cells. The scientists then imitated the onset of AML by injecting the mice with cancerous cells, and found the mice treated with the cryogel vaccine survived, while an entire control group died within 60 days. The first group was treated with a second dosage of AML cells after 100 days, and exhibited no sign of the disease.
Seeking to replicate the onset of AML more closely, the scientists then investigated the effects of the cryogel vaccine on bone marrow, which is where the disease originates. Here, in the bone marrow of the cryogel-vaccinated mice, they found large amounts of activated T cells and no signs of AML cells. Transplanting this bone marrow into new mice and dosing those healthy animals with AML cells again saw the the vaccine win out, with the transplant recipients surviving while an entire control group died within 30 days. The team says this result suggests the protection offered by the vaccine was “sustained and transferable.”
What followed were experiments where the cryogel vaccine was combined with the standard chemotherapy administered to AML patients. This brought about an increase in active T cells that was six times higher than the traditional course of treatment, which involves a liquid form of vaccine. Transplanting the bone marrow from the mice treated with the combination therapy into healthy mice saw the healthy animals exhibit no sign of AML for 14 days, and also survive a later dosage of AML cells, while a control group that didn’t receive the transplant died within 31 days.
“We are very excited about the performance of our AML vaccine, because it could finally provide long-term, relapse-free survival for AML patients, either to ‘clean up’ residual AML cells in the bone marrow following a stem cell transplant, or in older patients who cannot tolerate either transplants or high-dose chemo,” says co-author David Mooney.
The research was published in the journal Nature Biomedical Engineering.
Source: Wyss Institute
