Cue Biopharma, Cambridge, MA, USA.
BioKien LLC, Harpswell, ME, USA.
Sci Rep. 2021 Sep 28;11(1):19220. doi: 10.1038/s41598-021-98716-z.
Targeted pharmacologic activation of antigen-specific (AgS) T cells may bypass limitations inherent in current T cell-based cancer therapies. We describe two immunotherapeutics platforms for selective delivery of costimulatory ligands and peptide-HLA (pHLA) to AgS T cells. We engineered and deployed on these platforms an affinity-attenuated variant of interleukin-2, which selectively expands oligoclonal and polyfunctional AgS T cells in vitro and synergizes with CD80 signals for superior proliferation versus peptide stimulation.
靶向抗原特异性 (AgS) T 细胞的药物激活可能会绕过当前基于 T 细胞的癌症治疗中固有的局限性。我们描述了两种免疫治疗平台，用于选择性地将共刺激配体和肽-HLA (pHLA) 递送至 AgS T 细胞。我们在这些平台上设计并部署了一种亲和力减弱的白细胞介素-2 变体，该变体可在体外选择性扩增寡克隆和多功能 AgS T 细胞，并与 CD80 信号协同作用，从而在与肽刺激相比时具有更好的增殖能力。
