Peptide antibodies against blood cancer
Personalized therapy cured blood cancer in mice
Oleg Lischuk, N+1
The results of their work are published in the Proceedings of the National Academy of Sciences (James Torchia et al., Targeting lymphoma with precision using semisynthetic anti-idiotype peptibodies).
Stanford University researchers have chosen a variable site of the B-cell receptor, known as the idiotype, as a target for therapy. It is highly specific for tumor cells and differs from healthy B-lymphocytes. At the same time, the idiotype of tumor cells is individual for a particular patient, which makes the use of ready-made monoclonal antibodies impractical.
The researchers proposed to determine the structure of the idiotype in each patient. Then, in existing libraries, a small peptide with an affinity for this idiotype is selected, which is synthesized chemically. At this time, antibodies are taken from the patient and immutable fragments capable of crystallization (Fc) are separated from them. The synthesized peptide is chemically bound to Fc, obtaining a highly tumor-specific semi-synthetic peptide antibody (peptibody).
The principle of operation of the technique (James Torchia et al., PNAS, 2016)
During the in vitro experiment, peptide antibodies activated the enzyme of apoptosis caspase-3 in tumor cells within 24 hours, which led to their death. In addition, semisynthetic molecules activated the phagocytosis of tumor cells by macrophages, and they did it more strongly and specifically than monoclonal antibodies to a specific idiotype and the drug rituximab (monoclonal antibody to B-lymphocytic antigen CD20).
An experiment on immunodeficient mice with transplanted human lymphoma showed that the half-life of peptide antibodies from blood plasma is about 24 hours. Their four-time administration with an interval of a day led to complete resorption of tumors in all animals that received therapy, while mice from the control group experienced an intensive growth of neoplasms.
Resorption of the tumor on day 17 of therapy (Tx) and its growth in an untreated mouse (NT)
"Peptide antibodies are three times smaller than conventional antibodies by molecular weight, which ensures their better penetration into tissues; they allow one molecule to contain more than two antigen—binding sites, which increases avidity to the target," the researchers write.
Portal "Eternal youth" http://vechnayamolodost.ru
29.04.2016