Tom3 schreef op 11 oktober 2021 19:03:
Dit was de samenvatting van de laatste preklinische studie mbt AFM24 (gedateerd in juli 2021):
Epidermal growth factor receptor (EGFR)-targeted cancer therapy such as anti-EGFR monoclonal antibodies
and tyrosine kinase inhibitors have demonstrated clinical efficacy. However, there remains a medical need
addressing limitations of these therapies, which include a narrow therapeutic window mainly due to skin and
organ toxicity, and primary and secondary resistance mechanisms of the EGFR-signaling cascade (e.g., RASmutated colorectal cancer). Using the redirected optimized cell killing (ROCK®) antibody platform, we have
developed AFM24, a novel bispecific, IgG1-scFv fusion antibody targeting CD16A on innate immune cells,
and EGFR on tumor cells. We herein demonstrate binding of AFM24 to CD16A on natural killer (NK) cells and
macrophages with KD values in the low nanomolar range and to various EGFR-expressing tumor cells. AFM24
was highly potent and effective for antibody-dependent cell-mediated cytotoxicity via NK cells, and also
mediated antibody-dependent cellular phagocytosis via macrophages in vitro. Importantly, AFM24 was
effective toward a variety of EGFR-expressing tumor cells, regardless of EGFR expression level and KRAS/
BRAF mutational status. In vivo, AFM24 was well tolerated up to the highest dose (75 mg/kg) when
administered to cynomolgus monkeys once weekly for 28 days. Notably, skin and other toxicities were
not observed. A transient elevation of interleukin-6 levels was detected at all dose levels, 2–4 hours postdose, which returned to baseline levels after 24 hours. These results emphasize the promise of bispecific
innate cell engagers as an alternative cancer therapy and demonstrate the potential for AFM24 to effectively
target tumors expressing varying levels of EGFR, regardless of their mutational status.
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