Gel vaccine
Acute myeloid leukemia (AML) is a blood cancer that occurs in the bone marrow. Chemotherapy has been the standard treatment for AML for over 40 years, it often leads to remission, but it is extremely rare to completely eliminate cancer cells. Therefore, almost half of the patients have a relapse of the disease. Aggressive treatment after remission, such as high-dose chemotherapy or bone marrow transplantation, can reduce the likelihood of relapse, but patients with AML are so weakened that they do not tolerate these procedures well.
A group of researchers has developed an alternative treatment that has the potential to completely destroy AML cells. An innovative injectable vaccine based on biomaterial in combination with standard chemotherapy led to a complete and long-term recovery and the formation of immunity to AML in mice. The study was conducted at Harvard University.
The group had previously developed vaccines against solid tumors, and now the researchers decided to test the same technology for the treatment of blood tumors, in particular, AML.
The AML vaccine consists of a cryogel matrix that contains biomolecules to attract and activate the body's dendritic cells. They can initiate an immune response against cancer cells and provide long-term immunity to the disease. Source: Wyss Institute.
Tricky cryogel
The new vaccine is a small–sized cryogel frame made of two materials - polyethylene glycol and alginate, which were sewn together to form a matrix. Biomolecules of two cytokines (GM-CSF and CpG-ODN) were embedded in the scaffold to attract the body's dendritic cells and activate them. The vaccine also contains one or more antigens specific to AML cells – fragments of dead AML cells or part of the WT-1 protein that AML cells express on their surface). Activated dendritic cells take antigens from the vaccination site and present them to T cells, forcing them to find and destroy AML cells. There is recovery and protection from relapse.
To test the effectiveness of the cryogel vaccine, it was injected under the skin of healthy mice. This led to an increase in the number of activated T-lymphocytes. The vaccine was then administered to mice who received an injection of AML cells to simulate the onset of the disease. Mice that received the liquid form of the vaccine or cryogel without biomolecules died within 60 days, while mice that received the cryogel vaccine survived. The surviving animals were re-injected with a portion of AML cells after 100 days, and they did not develop signs of the disease. This proves that the vaccine has successfully protected them from relapse.
Since AML originates from the bone marrow and cancer cells can "hide" there to avoid the effects of chemotherapy, the group analyzed the bone marrow of mice. In mice vaccinated with cryogel, a large number of active T-lymphocytes were found and there were no traces of AML cells. When the bone marrow of these mice was transplanted into healthy rodents and then injected with AML cells, all the recipient mice survived, while the control group of mice died from AML within 30 days. The result indicates the stability of the immune defense against AML.
An unexpected find
In order to more accurately simulate the clinical scenario of AML in humans, the team injected a cryogel vaccine into mice that had AML simultaneously with a standard course of chemotherapy. The response of activated T-lymphocytes was six times higher in mice receiving combination therapy than in mice receiving chemotherapy and the liquid form of the vaccine. That is, cryogel was a much more effective means of delivering activating biomolecules to the immune system.
Surprisingly, in combination with chemotherapy, the cryogel vaccine was effective even without an antigenic component. As it turned out, the vaccine-activated dendritic cells collected fragments of tumor cells destroyed by chemotherapy and used them to initiate T-lymphocytes.
Work on the cryogel vaccine continues in several directions. Researchers are exploring how it can be combined with sequencing technology to identify antigens specific to a particular patient's cancer and create a highly personalized vaccine, as well as exploring potential interactions with T cells.
Article by N.J.Shah et al. A biomaterial-based vaccine eliciting durable tumour-specific responses against acute myeloid leukaemia is published in the journal Nature Biomedical Engineering.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Wyss Institute: A solid vaccine for liquid tumors.