Monoclonal antibodies applied in treatment for hematological malignancies

Abstract

Monoklonska protutijela su protutijela monovalentnog afiniteta (vežu isti epitop) nastala iz klonova jedinstvene roditeljske B-stanice. Otkriće tehnologije hibirdoma stanica omogućilo je dobivanje mišjih monoklonskih protutijela na željeni antigen, a daljnjim napretkom genetičkog inženjerstva i tehnologije rekombinantne DNA moguće je dobiti kimerna, humanizirina te potpuno humana protutijela. Humanizacijom je poboljšana učinkovitost te je produžen poluživot protutijela. U medicini se koriste kao oblik imunoterapije za liječenje autoimunih bolesti, infekcija i tumora. Monoklonska su protutijela novost u liječenju hematoloških maligniteta, tumora mijeloidne i limfoidne stanične linije, uz uobičajene terapije kao što su kemoterapija, radioterapija i transplantacija hematopoetskih matičnih stanica. Zahvaljujući njihovoj specifičnosti prema tumorskim antigenima i učinku na tumorske stanice (aktivacija ADCC, CDC, indukcija apoptoze i blokiranje vezanja liganda), odlična su opcija u liječenju malignih bolesti. Postoje dvije vrste antigena koje prepoznaju: antigeni specifični za staničnu liniju (LSA) koji se nalaze na određenim stanicama prilikom različitih diferencijacijskih stadija te antigeni nespecifični za staničnu liniju (NLSA) koji nisu ograničeni na pojedinu staničnu liniju. Prvo odobreno monoklonsko protutijelo bio je rituximab, anti-LSA protutijelo na CD20, koje se pokazalo učinkovito u liječenju nekih B-staničnih maligniteta. Od tada, mnoga monoklonska protutijela već su odobrena od strane FDA ili se testiraju u kliničkim istraživanjima.Monoclonal antibodies are antibodies with monovalent affinity (they bind to the same epitope) produced by clones of a unique parent B-cell. Discovery of hybridoma technology made it possible to produce murine monoclonal antibodies specific to known antigens and with further advances in genetic engineering and recombinant DNA technology it was possible to produce chimeric, humanized and completely human antibodies. Humanization of the antibody has improved its efficacy and prolonged its half-life. In medicine they are used as a form of immunotherapy for autoimmune diseases, infections and tumors. Monoclonal antibodies are a novelty in treatment of hematological malignancies, tumors of myeloid and lymphoid cell lineages, alongside common therapies as chemotherapy, radiotherapy and transplantation of hematopoietic stem cells. Due to their specificity for tumor-associated antigens and the effect they have on the tumor cells (activation of ADCC, CDC, induction of apoptosis or blocking ligand binding), they are a great option in treatment of malignancies. There are two types of antigens they recognize: lineage specific antigens (LSA) that are present at different differentiation steps of a certain cell lineage, and non-lineage specific antigens (NLSA) that aren’t restricted to a single cell lineage. The first approved monoclonal antibody was rituximab, an anti-LSA antibody targeting CD20, which has shown to be effective in treating some B-cell malignancies. Since then, many monoclonal antibodies have been approved by the FDA or are being tested in clinical trials