In de afgelopen decennia is op monoklonale antilichamen gebaseerde kankerbehandeling gevestigd als een van de meest succesvolle behandelingsstrategieën voor solide tumoren en bloedkankers. Zoals de naam al aangeeft, zijn monoklonale antilichamen (mAbs) antilichamen gemaakt van gekloonde cellen afgeleid van cellen van één ouder en delen daarom dezelfde aminozuursequentie. Multipel myeloom is een relatief veel voorkomende vorm van bloedkanker, en de Universiteit van Osaka in Japan heeft een nieuw type immunotherapie ontwikkeld om deze ziekte te behandelen.
Volgens rapporten zijn er ongeveer 18,000 patiënten met multipel myeloom in Japan. Hoewel het behandelingsniveau aanzienlijk is verbeterd en de overlevingsperiode van de patiënt is verlengd, is volledige genezing buitengewoon moeilijk en vatbaar voor terugval.
CAR T-celtherapie
Molecules sufficient to induce an immune response to produce antibodies-cancer-specific mutations of cell surface proteins are excellent targets. However, mAb therapy against this antigen is impractical because these proteins have great diversity within and between individual tumors, which makes it difficult to identify new cancer-specific target antigens. However, researchers centered on Osaka University in Japan have discovered cancer-specific antigens formed by protein modification, such as glycosylation (the connection of the sugar moiety to the protein) or conformational changes. The research team believes that the new epitope is part of the antigen recognized by immune cells, and can be found by thoroughly searching for cancer-specific mAbs and identifying the antigens it recognizes. figure 2. Overview of CAR T-celtherapie. Source: Osaka University “We applied this strategy to identify new therapeutic targets for multiple myeloma (MM), Naoki Hosen, the study’s lead author, recently published in Nature Medicine.” Despite progress in MM treatment, relapses continue Is common, so new treatments are needed, including mAb-based treatments. The research team screened more than 10,000 anti-MM mAb clones and identified MMG49 as a mAb that specifically recognizes integrin β7, a cell surface receptor that promotes cell-extracellular matrix adhesion. MMG49 reacts with MM cells , But there are no other bone marrow cell types in the MM patient samples. This prompted the researchers to design a CAR fused with the MMG49 fragment. The MMG49 CAR T produced was found to have an anti-MM effect without destroying normal blood cells. “Our results also show that The active conformation of integrin β7 can be used as an immunotherapy target for MM, ”said study co-author Yukiko Matsunaga. Therefore, even if the expression of the protein itself is not cancer-specific, there are still other cancer immunotherapy targets in many cell surface proteins These targets have not yet been discovered in conformational changes, which is very reasonable. Figure 3. Anti-myeloma activity of MMG49 CAR T cells. Credit: Fred Hutch, Osaka University, researchers provide complex immunotherapy for recurrent immunotherapy, possible Treatment of relapsed leukemia.
