Hulskof schreef op 22 april 2021 13:18:
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Larry Hsin, ook de moeite waard om te volgen, schrijft er dit over:
AFMD and FATE
Rationale for combination of CAR-NK and NK engagers
Besides killing tumour target cells in the CAR-dependent manner, CAR-NK cells can potentially eliminate cancer cells in a CAR-independent manner. CAR-NK cells still possess their natural cytotoxic activity against tumour cells and can be activated through CAR-independent mechanism, such as NCRS, NKG2D, co-stimulatory receptor DNAM-1 (CD226), and certain activating KIRS (KIR2DS1, KIR2DS4 and KIR2DL4). Moreover, NK cells can eliminate tumour cells through CD16-mediated ADCC. Thus, CAR-modified NK cells may be able to efficiently eradicate a heterogeneous tumour in which some tumour cells do not express CAR-targeted antigen, via both CAR-dependent and NK cell receptor-dependent mechanisms.
The combination with antibodies targeting different tumour-associated antigens is another strategy to improve the efficacy of CAR-NK cell therapy. NK cells express CD16 and exert ADCC mediated tumour killing. Promising results have been obtained in patients with neuroblastoma or refractory NHL receiving allogeneic NK cells following administration of anti-GD2 or anti CD20 antibody. However, cytokine activation or target cell stimulation usually lead to marked decreases in CD16 expression on NK cells, which impairs ADCC-mediated tumour killing. A possible approach is to genetically engineer NK cells to stably express a non-cleavable CD16. An IPSC-derived CAR-NK cell product, FT596, is engineered with three active anti-tumour components including a CD19-CAR, a novel high-affinity and non-cleavable CD16, and an IL-15 receptor fusion protein. Preclinical data showed that FT596 not only induced durable tumour regression and extended survival in humanized mice with CD19" lymphoma, but also exhibited enhanced killing of the CD20 lymphoma cells in vivo when combined with the anti-CD20 antibody rituximab, compared to rituximab alone. These data suggest that FT596 possesses multi-antigen targeting function when administered with therapeutic antibodies, and thus effectively overcome tumour resistance due to loss of CD19 antigen.
AFMD's NK engagers are more component and powerful in inducing ADCC compare to the regular antibodies, including rituximab.
Zo bezien heeft Fate Affimed harder nodig dan andersom...