研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

Peptide emulsions在不完全Freund佐剂中创建有效的育种场,促进系统性CD4+和CD8+ T细胞外出,用于癌症免疫治疗。

Peptide emulsions in incomplete Freund's adjuvant create effective nurseries promoting egress of systemic CD4+ and CD8+ T cells for immunotherapy of cancer.

发表日期:2022 Sep
作者: Marit M Melssen, Caroline T Fisher, Craig L Slingluff, Cornelis J M Melief
来源: Journal for ImmunoTherapy of Cancer

摘要:

自从开发以来,水油乳化物不完全弗氏佐剂(IFA)已被用作预防和治疗疫苗的佐剂。新一代高度纯化的佐剂调节剂Montanide不完全seppic佐剂(ISA)-51和Montanide ISA-720已经开发出来,以减少毒性。Montanide佐剂一般被认为是安全的,不良事件主要是与抗原和佐剂剂量相关的注射部位反应(ISRs)。Montanide ISA-51或ISA-720的肽疫苗能够诱导高抗体滴度和持久的效应T细胞反应。然而,效率高的T细胞反应取决于肽对表现主要组织相容性复合物I类分子,CD4 + T细胞的帮助和/或共刺激水平的亲和力。事实上,在治疗癌症疫苗的情况下,CD4 + T细胞表位的存在似乎对引起强大和持久的全身T细胞反应至关重要。另外,包括寡聚核苷酸受体配体的使用可以进一步增加反应的强度和持久性。需要进行处理步骤才能有效完成树突状细胞(DCs)的抗原呈递的扩展肽可以帮助避免除DC以外的有核细胞的其它免疫原呈递。基于最近的临床试验结果,使用Montanide ISA-51佐剂乳化物制备的治疗性肽基癌症疫苗,只要在CD8 + T细胞表位中添加充足的肿瘤特异性CD4 + T细胞帮助,就能引起强大的抗肿瘤免疫反应。联合PD-1 T细胞检查点抑制剂,化疗或其他免疫调节药物的治疗可能会解决局部和全身免疫抑制机制,进一步增强IFA及其现代变体治疗性癌症肽疫苗的功效。盲目的随机安慰剂对照试验对于明确证明临床疗效至关重要。矿物油基佐剂用于预防性疫苗,以应对传染病的传播和严重程度,能够诱导免疫反应,但需要更多的研究来减少毒性。 ©作者(或其雇主)2022年。在CC BY-NC下允许再次使用。没有商业再利用。由BMJ出版。
Water-in-oil emulsion incomplete Freund's adjuvant (IFA) has been used as an adjuvant in preventive and therapeutic vaccines since its development. New generation, highly purified modulations of the adjuvant, Montanide incomplete seppic adjuvant (ISA)-51 and Montanide ISA-720, were developed to reduce toxicity. Montanide adjuvants are generally considered to be safe, with adverse events largely consisting of antigen and adjuvant dose-dependent injection site reactions (ISRs). Peptide vaccines in Montanide ISA-51 or ISA-720 are capable of inducing both high antibody titers and durable effector T cell responses. However, an efficient T cell response depends on the affinity of the peptide to the presenting major histocompatibility complex class I molecule, CD4+ T cell help and/or the level of co-stimulation. In fact, in the therapeutic cancer vaccine setting, presence of a CD4+ T cell epitope seems crucial to elicit a robust and durable systemic T cell response. Additional inclusion of a Toll-like receptor ligand can further increase the magnitude and durability of the response. Use of extended peptides that need a processing step only accomplished effectively by dendritic cells (DCs) can help to avoid antigen presentation by nucleated cells other than DC. Based on recent clinical trial results, therapeutic peptide-based cancer vaccines using emulsions in adjuvant Montanide ISA-51 can elicit robust antitumor immune responses, provided that sufficient tumor-specific CD4+ T cell help is given in addition to CD8+ T cell epitopes. Co-treatment with PD-1 T cell checkpoint inhibitor, chemotherapy or other immunomodulatory drugs may address local and systemic immunosuppressive mechanisms, and further enhance efficacy of therapeutic cancer peptide vaccines in IFA and its modern variants. Blinded randomized placebo-controlled trials are critical to definitively prove clinical efficacy. Mineral oil-based adjuvants for preventive vaccines, to tackle spread and severity of infectious disease, induce immune responses, but require more studies to reduce toxicity.© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.