Simlukafusp alfa

Simlukafusp alfa (FAP-IL2v) is a tumor-targeting immunocytokine and a human antibody with antitumor activity and immunostimulatory properties. It enhances the in vitro and in vivo activity of therapeutic antibodies that mediate antibody-dependent or T-cell-dependent cytotoxicity (TDCC) and inhibit the programmed death-ligand 1 (PD-L1) checkpoint. Simlukafusp alfa is intended for use in the study of solid tumors and the tumor immune microenvironment.

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

The binding constants of Simlukafusp alfa for IL-2Rβγ and FAP receptors from different species are 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 vitro, Simlukafusp alfa (0–100 nM; treated for 5 days) activated CD4+ and CD8+ T cells as well as NK cells, but did not preferentially activate Tregs. Furthermore, Simlukafusp alfa (0–100 nM) enhanced Cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) and Cibisatamab-mediated T-cell-dependent cytotoxicity (TDCC) in vitro. [1]
Methods: Human primary CD4⁺ T cells were isolated, coated with anti-CD3 (0.125 μg/mL), and stimulated with Simlukafusp alfa (0.4/4.0/40.4 nM) for 3 days; IL-2 levels in the supernatant were measured by ELISA.
Results: Simlukafusp alfa promoted IL-2 secretion in a dose-dependent manner. [2]
Methods: Human PBMCs were labeled with Far Red dye and seeded into anti-CD3-coated culture plates. They were cultured for 96 hours with Simlukafusp alfa (starting concentration 100 nM, 3-fold dilution gradient), and the proliferation rates of CD4⁺ and CD8⁺ T cells were measured by flow cytometry.
Results: Simlukafusp alfa significantly promoted the proliferation of CD4⁺ and CD8⁺ T cells.[2]

In a mouse model of human cancer, Simlukafusp alfa administered intravenously at a dose of 1 mg/kg once weekly for 4 consecutive weeks demonstrated significant efficacy when used in combination with a therapeutic antibody. [1]
Methods: A tumor model was established in humanized NOG mice by co-transplanting LoVo cells and human PBMCs. When tumor volume reached 50 mm³, Simlukafusp alfa was administered intraperitoneally at a dose of 10 mg/kg on days 3, 7, 11, and 14–15 post-tumor implantation. Tumor volume was monitored using a caliper.
Results: Simlukafusp alfa demonstrated significant antitumor effects, had no significant impact on body weight, and exhibited good safety. [2]
Methods: Rhesus monkeys were administered Simlukafusp alfa intravenously (10/50/200 mg/kg, once weekly for a total of 5 doses), followed by a 4-week recovery period; clinical symptoms, body weight, hematology, biochemistry, and histopathology were monitored.
Results: At the highest dose, Simlukafusp alfa showed no drug-related adverse reactions, organ damage, immunotoxicity, or pathological changes, demonstrating excellent tolerability. [2]

Human

Monoclonal

Unconjugated