Latikafusp (AMG 256) is a bifunctional fusion protein comprising a PD-1-targeting antibody and IL-21 mutein designed to deliver IL-21 pathway stimulation to PD-1+ cells. Latikafusp is designed to prime and extend the activity of cytotoxic and memory T cells and induce anti-tumor immunity. Latikafusp has the potential for solid tumors research.Latikafusp may lead to the development of immunogenicity-mediated responses.
Latikafusp (5 mg/kg; administered on days 1 and 15; i.v.) induces significant immunogenicity and persensitivity in cynomolgus monkeys[3]. Latikafusp (10, 30 mg/kg; Weekly doses over three weeks; i.v.) activates both classical and alternative complement pathways[3]. Latikafusp (10, 30 mg/kg; Weekly doses over three weeks; i.v.) causes cynomolgus monkeys in all dose groups to show strong antibody responses, suggesting that the drug has high immunogenicity[3].
References:
[1]. Greg Durm, et al. Abstract CT205: Design and rationale of a phase 1 study evaluating AMG 256, a novel, targeted, PD-1 antibody x IL-21 mutein bifunctional fusion protein, in patients with advanced solid tumors. Clin Cancer Res. 2022 Apr 1;28(7):1294-1301.
[2]. Gregory Durm, et al. 417 Design and rationale of a phase 1 study evaluating AMG 256, a novel, targeted, IL-21 receptor agonist and anti-PD-1 antibody, in patients with advanced solid tumors. Journal for ImmunoTherapy of Cancer, 2020, 8(Suppl 3). [3]. Kroenke Met al. Translatability of findings from cynomolgus monkey to human suggests a mechanistic role for IL-21 in promoting immunogenicity to an anti-PD-1/IL-21 mutein fusion protein. Front Immunol. 2024 Jan 26;15:1345473.