Aljohani Salwa, Edmonds Alex G, Castelletto Valeria, Seitsonen Jani, Hamley Ian W, Symonds Peter, Brentville Victoria A, Durrant Lindy G, Mitchell Nicholas J
School of Chemistry, University of Nottingham, University Park, Nottingham, UK.
School of Chemistry, Pharmacy and Food Biosciences, University of Reading, Reading, UK.
J Pept Sci. 2025 Jun;31(6):e70022. doi: 10.1002/psc.70022.
Peptide-based vaccines, formulated with an appropriate adjuvant, offer a versatile platform for targeted cancer immunotherapy. While adjuvants are usually coadministered for nucleic acid and protein vaccines, synthetic peptide antigens afford a more effective opportunity to covalently and regioselectively graft immunostimulatory motifs directly onto the antigen scaffold to yield self-adjuvanting vaccines. Herein, we explore the synthesis of two tissue-restricted cancer-testis antigens (CTAs); New York oesophageal cell carcinoma 1 (NY-ESO-1) and B melanoma antigen 4 (BAGE4), both carrying the toll-like receptor (TLR) agonist, PamCys. These constructs were evaluated in vivo along with a lipid nanoparticle (LNP) preparation of the underexplored BAGE4 melanoma antigen.
基于肽的疫苗与合适的佐剂一起配制，为靶向癌症免疫治疗提供了一个多功能平台。虽然佐剂通常与核酸和蛋白质疫苗共同给药，但合成肽抗原提供了一个更有效的机会，可将免疫刺激基序直接共价且区域选择性地接枝到抗原支架上，从而产生自佐剂疫苗。在此，我们探索了两种组织限制性癌症睾丸抗原（CTA）的合成；纽约食管癌细胞癌1（NY-ESO-1）和B黑色素瘤抗原4（BAGE4），两者都携带Toll样受体（TLR）激动剂PamCys。这些构建体与未充分研究的BAGE4黑色素瘤抗原的脂质纳米颗粒（LNP）制剂一起在体内进行了评估。
