T-cell triggering by CD3- and CD28-binding molecules linked to a human virus-modified tumor cell vaccine

Haas C; Lulei M; Fournier P; Arnold A; Schirrmacher V

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T-cell triggering by CD3- and CD28-binding molecules linked to a human virus-modified tumor cell vaccine

机译：由与人类病毒修饰的肿瘤细胞疫苗相关的CD3和CD28结合分子触发T细胞

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The aim was to develop T cell costimulatory molecules that are broadly applicable to augment anti-tumor immune responses upon application of a virus-modified tumor vaccine to cancer patients. We generated recombinant bispecific single-chain antibodies with one specificity directed against the CD3 or the CD28 antigen on human T cells and the other against the viral target molecule hemagglutinin-neuraminidase (HN) of Newcastle Disease Virus (NDV). By re-directing unstimulated primary human T cells against HN-expressing NDV-infected tumor cells, the bispecific molecule bsHN-CD3 cross-linked effector and target cells and rapidly induced cytotoxicity at nanomolar concentrations. The bsHN-CD28 molecule exerted T cell co-stimulatory function. Maximal T cell activation was achieved with tumor cells infected by NDV and modified with both new stimulatory molecules. This was revealed by T cell proliferation, upregulation of CD69 and CD25 and by release of cytokines, interferons and chemokines. The new molecules combine high-effectivity with specificity and safety.

机译：目的是开发广泛适用于在将病毒修饰的肿瘤疫苗应用于癌症患者后增强抗肿瘤免疫反应的T细胞共刺激分子。我们生成了重组双特异性单链抗体，其一种针对人T细胞上的CD3或CD28抗原，另一种针对新城疫病毒（NDV）的病毒靶分子血凝素神经氨酸酶（HN）。通过将未刺激的原代人T细胞针对表达HN的NDV感染的肿瘤细胞进行重定向，双特异性分子bsHN-CD3交联了效应细胞和靶细胞，并在纳摩尔浓度下迅速诱导了细胞毒性。 bsHN-CD28分子发挥T细胞共刺激功能。用NDV感染并用两种新的刺激性分子修饰的肿瘤细胞可实现最大的T细胞活化。 T细胞增殖，CD69和CD25上调以及细胞因子，干扰素和趋化因子的释放揭示了这一点。新分子将高效性与特异性和安全性结合在一起。

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《Vaccine》 |2005年第19期|共15页
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Haas C; Lulei M; Fournier P; Arnold A; Schirrmacher V;
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中图分类卫生标准、卫生检查、医药管理;
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1. T-cell triggering by CD3- and CD28-binding molecules linked to a human virus-modified tumor cell vaccine [J] . Haas C, Lulei M, Fournier P, Vaccine . 2005,第19期

机译：由与人类病毒修饰的肿瘤细胞疫苗相关的CD3和CD28结合分子触发T细胞
2. The mouse chorionic gonadotropin beta-subunit-like (muCG beta l) molecule produced by tumor cells elicits the switch of T-cell immunity response from T(H)2 to T(H)1 in mice immunized with DNA vaccine based on rhesus monkey homologous CG beta (rmCG be [J] . Shi SQ, Peng JP, Xu L, The journal of gene medicine . 2005,第1期

机译：肿瘤细胞产生的小鼠绒毛膜促性腺激素β-亚基样（muCGβ1）分子引发了用基于恒河猴的DNA疫苗免疫的小鼠中T细胞免疫应答从T（H）2转变为T（H）1的过程同源CG beta（rmCG be
3. Concordant Proficiency in Measurement of T-Cell Immunity in Human Immunodeficiency Virus Vaccine Clinical Trials by Peripheral Blood Mononuclear Cell and Enzyme-Linked Immunospot Assays in Laboratories from Three Continents [J] . Mark J. Boaz, Peter Hayes, Tony Tarragona, Clinical and vaccine immunology: CVI . 2009,第2期

机译：在来自三个大洲的实验室中通过外周血单核细胞和酶联免疫斑点法测定人类免疫缺陷病毒疫苗临床试验中T细胞免疫的一致性
4. Photodynamic therapy stimulates anti-tumor immune response in mouse models: the role of regulatory T-cells, anti-tumor antibodies, and immune attack on brain metastases [C] . Fatma Vatansever, Masayoshi Kawakubo, Hoon Chung, Biophotonics and immune responses VIII . 2013

机译：光动力疗法在小鼠模型中刺激抗肿瘤免疫反应：调节性T细胞，抗肿瘤抗体的作用以及对脑转移瘤的免疫攻击
5. Carbohydrate derived nanoplatforms as tools for lectin isolation, and delivery of cytotoxic T-cell peptide epitopes for cytotoxic T-cell mediated tumor immunotherapy. [D] . Kavunja, Herbert Wanjala. 2015

机译：碳水化合物衍生的纳米平台作为凝集素分离的工具，以及细胞毒性T细胞肽表位的递送，用于细胞毒性T细胞介导的肿瘤免疫治疗。
6. Concordant Proficiency in Measurement of T-Cell Immunity in Human Immunodeficiency Virus Vaccine Clinical Trials by Peripheral Blood Mononuclear Cell and Enzyme-Linked Immunospot Assays in Laboratories from Three Continents [O] . Mark J. Boaz, Peter Hayes, Tony Tarragona, 2009

机译：在来自三个大洲的实验室中通过外周血单核细胞和酶联免疫斑点法测定人类免疫缺陷病毒疫苗临床试验中T细胞免疫的一致性
7. Gemcitabine depletes regulatory T-cells in human and mice and enhances triggering of vaccine-specific cytotoxic T-cells [O] . Rettig, L, Seidenberg, S, Parvanova, I, 2011

机译：吉西他滨消耗人和小鼠中的调节性T细胞并增强疫苗特异性细胞毒性T细胞的触发
8. FDA Briefing Document. Vaccines and Related Biological Products Advisory Committee Meeting September 19, 2012: Cell Lines Derived from Human Tumors for Vaccine Manufacture. [R] . 2012

机译：FDa简报文件。疫苗和相关生物制品咨询委员会会议2012年9月19日：来自人类肿瘤的细胞系用于疫苗生产。

T-cell triggering by CD3- and CD28-binding molecules linked to a human virus-modified tumor cell vaccine

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