Personalized nanovaccine cured mice of cancer
Oleg Lischuk, N+1
American scientists have developed a method of effective delivery of peptide antigenic vaccines for personalized cancer therapy. In the experiment, the use of this method caused a complete cure of most of the experimental mice. The results of the work are published in the journal Nature Materials (Kuai et al., Designer vaccine nanodiscs for personalized cancer immunotherapy).
Peptide vaccines against cancer are antigens specific to the tumor of a particular patient (neoantigens) and, accordingly, produced personally based on the results of sequencing of tumor DNA. Due to the high safety of use and the comparative simplicity of production, many research teams are engaged in their research, but it has not yet been possible to achieve sufficient effectiveness in clinical trials. The reason for this is the poor penetration of peptide neoantigens and adjuvants (drugs that enhance their effect) into the lymph nodes and, as a consequence, insufficient activation of cytotoxic T-lymphocytes under their action.
The staff of the University of Michigan with colleagues from other research centers proposed to deliver antigens with adjuvants to nanoparticles resembling high-density lipoproteins (HDL) in structure. This is one of the varieties of protein-lipid complexes that serve for the transport of fats (in particular, cholesterol) in the blood.
The nanoparticles developed by scientists consist of three components: the first – an analog of apolipoprotein A (HDL component) – serves as the material of the nanoparticle; the second – cholesterol–bound dinucleotide CpG - ensures its promotion to the lymph nodes and the third – personalized neoantigens that trigger an immune response. Such a nanoparticle has the shape of a disk with a diameter of about 10 nanometers.
Experiments have shown that this delivery method causes stable presentation of the neoantigen by dendritic cells and their maturation, which, in turn, leads to the appearance of a large number of activated cytotoxic T-lymphocytes specific to the tumor antigen (47 times more than when using soluble peptide neoantigens).
The principle of operation of the methodology
These T-lymphocytes effectively recognized and destroyed cancer cells in the peripheral tissues of mice. The addition of CTLA-4 and PD-1 immune checkpoint inhibitors to such immunotherapy after 10 days led to complete resorption of colon adenocarcinoma in about 88 percent of animals (versus about 25 percent in the case of soluble antigens) and melanoma in about 90 percent of animals (versus about 38 percent with soluble antigens). Repeated administration of similar cancer cells after 70 days did not lead to the development of tumors, that is, immunity developed to them.
Currently, scientists are engaged in reproducing the technology in larger animals so that, if successful, they can proceed to clinical trials. To develop and bring the technology to market, the university has established a spin-off of EVOQ Therapeutics.
Immunotherapy is currently the most promising direction in the experimental treatment of cancer. In addition to neoantigens , vaccines have been developed and are being tested in the form of RNA lipoplexes, as well as various genetically modified hematopoietic cells and T-lymphocytes.
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09.01.2017