Although the role of senescence in many physiological and pathological processes is becoming more identifiable, many aspects of senescence are still enigmatic. A special attention is paid to the role of this phenomenon in tumor development and therapy. This review mainly deals with a large spectrum of oncological issues, beginning with therapy-induced senescence and ending with oncogene-induced senescence. Moreover, the role of senescence in experimental approaches, such as primary cancer cell culture or reprogramming into stem cells, is also beginning to receive further consideration. Additional focus is made on senescence resulting from mitotic catastrophe processes triggered by events occurring during mitosis and jeopardizing chromosomal stability. It has to be also realized that based on recent findings, the basics of senescent cell property interpretation, such as irreversibility of proliferation blockade, can be undermined. It shows that the definition of senescence probably requires updating. Finally, the role of senescence is lately more understandable in the immune system, especially since senescence can diminish the effectiveness of the chimeric antigen receptor T-cell (CAR-T) therapy. In this review, we summarize the current knowledge regarding all these issues.

STreSzczenieOstatnio dokonuje się przełom w immunoterapiach. Rozwój produktów leczniczych terapii zaawansowanej (advanced therapy medicinal product -ATMP) jest tego dobitnym przykładem. Terapia CAR-T (chimeric antigen receptors T cell therapy) jest efektem współpracy biotechnologów, onkologów i immunologów. W artykule poruszono problematykę związaną z rozwojem technologii CAR-T. Omówiono podstawy projektowania CAR-T i mechanizm działania tej terapii. Przedstawiono generalne zasady tworzenia kolejnych generacji CAR-T. Wskazano sukcesy terapii opartej na CAR-T, związane głównie z leczeniem pacjentów z białaczkami i chłoniakami. Opisano główne cele molekularne CAR-T, takie jak CD19 czy CD22. Jednocześnie zwrócono uwagę na dotychczasowe ograniczenia dotyczące terapii pacjentów z guzami litymi. Opisano przykładowy cel dla terapii guzów litych, za jaki uznaje się zmutowany receptor dla naskórkowego czynnika wzrostu EGFRvIII. Wskazano jednak, na jakie trudności natrafia terapia przeciwko komórkom EGFRvIII-pozytywnym. Przedstawiono również rosnące znaczenie PSMA i GD2 jako celów dla CAR-T. Opisano nowe trendy w obrębie tej technologii, takie jak CAR-M. Scharakteryzowano potencjalne zastosowane CAR-T w chorobach nienowotworowych, w tym alergiach lub chorobach zakaźnych z włączeniem COVID-19. Słowa kluczoweCAR-T, białaczka, chłoniak, guzy lite, EGFRvIII, alergia, astma, zwłóknienie serca, COVID-19, choroby zakaźne.abSTracT Recently, there has been a breakthrough in immunotherapy. The development of the advanced therapy medicinal product (ATMP) is a striking example of that. Chimeric antigen receptors T cell therapy (CAR-T therapy) is the result of cooperation between biotechnologists, oncologists and immunologists. This article deals with the issues related to the development of CAR-T technology. The basics of CAR-T design and the mechanism of this therapy action are discussed. Its successes were indicated mainly in the treatment of patients with leukemias and lymphomas. EGFRvIII as an exemplary target for the therapy of solid tumors is described. However, it was pointed out what difficulties the therapy against mutated variant of epidermal growth factor receptor EGFRvIII-positive cells encounters. The growing importance of PSMA and GD2 as targets for CAR-T was also pointed out. New trends in this technology, such as the next generations of CAR-T and development of Amelia Kierasińska, Damian Ciunowicz oraz Marta Węgierska są ex aequo pierwszymi autorami tej pracy.