Simlukafusp alfa (FAP-IL2v) is a tumor-targeting immune cytokine, a human IgG1 antibody, with antitumor activity and immunostimulatory properties that potentiate in vitro and in vivo activity of therapeutic antibodies mediating antibody-dependent or T-cell-independent cytotoxicity (TDCC) and programmed death ligand 1 (PD-L1) checkpoint inhibition.

FAP (cynomolgus monkeys):0.23 nM (KD), FAP (human):0.3 nM (KD), FAP (mouse):0.5 nM (KD), IL-2Rβγ (mouse):660 pM (KD), IL-2Rβγ (cynomolgus monkeys):80 pM (KD), IL-2Rβγ (human):43 pM (KD)

The binding constants of Simlukafusp alfa to IL-2Rβγ and FAP receptors of different species were as follows: huIL-2Rβγ: 43 pM; cyIL-2Rβγ: 80 pM; muIL-2Rβγ: 660 pM; huFAP: 0.3 nM; cyFAP: 0.23 nM; muFAP: 0.5 nM.
In in vitro experiments, Simlukafusp alfa (0-100 nM; 5 days of treatment) was able to activate CD4+ and CD8+ T cells as well as NK cells, but did not preferentially activate Tregs. furthermore, Simlukafusp alfa (0-100 nM) potentiated Cetuximab-mediated antibody-dependent cellular cytotoxicity in vitro (ADCC ) and Cibisatamab-mediated T cell-dependent cytotoxicity (TDCC). [1]

In a mouse model of human cancer, Simlukafusp alfa administered intravenously at a dose of 1 mg/kg once a week for 4 weeks demonstrated significant efficacy when combined with therapeutic antibodies. [1]

Human

Monoclonal

Unconjugated