Anti-CD3/anti-epidermal growth factor receptor-bispecific antibody retargeting of lymphocytes against human neoplastic keratinocytes in an autologous organotypic culture model.
Anti-CD3/anti-epidermal growth factor receptor-bispecific antibody retargeting of lymphocytes against human neoplastic keratinocytes in an autologous organotypic culture model.
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在自体器官培养模型中，抗 CD3/抗表皮生长因子受体双特异性抗体针对人肿瘤性角质形成细胞重新靶向淋巴细胞。
DOI：
10.1016/s0002-9440(10)64355-6
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
N. Jacobs
中科院分区：
文献类型：
--
作者：
I. Renard;D. Mezzanzanica;S. Canevari;S. Ferrini;J. Boniver;P. Delvenne;N. Jacobs
局部细胞免疫缺陷已被描述为几种肿瘤，包括人乳头瘤病毒（HPV）相关的宫颈癌。这一观察结果表明，恢复细胞免疫的免疫操作具有潜在的治疗益处。在这里，我们评估了双特异性单克隆抗体（bimAbs）在自体三维培养模型（器官型培养）中引导T细胞对抗体外由HPV转化的角质形成细胞的能力。选择表皮生长因子受体（EGFR）作为抗cd3 /抗EGFR双抗的靶标，是因为它在许多恶性上皮病变中过表达，而仅在正常鳞状上皮的基底层弱表达。有趣的是，在器官型培养中，EGFR的表达模式与体内观察到的相似。CD3/EGFR双抗重靶向T细胞裂解hpv转化细胞系的能力在单层培养中得到证实。在自体器官型培养中，当向培养中加入活化淋巴细胞和bimAbs时，观察到凋亡的HPV+角质形成细胞增加，HPV+器官型培养细胞的厚度显著减少，而正常角质形成细胞的器官型培养没有明显影响。这些数据与异体模型中获得的数据相似。这些结果表明，CD3-EGFR双抗重靶向淋巴细胞在恶性上皮病变的免疫治疗方案中可能有用。
Local cellular immune defects have been described in several tumors including human papillomavirus (HPV)-associated cervical cancer. This observation suggests the potential therapeutic benefit of immune manipulations that restore cellular immunity. Here, we evaluated the ability of bispecific monoclonal antibodies (bimAbs) to redirect T cells against keratinocytes transformed in vitro by HPV in an autologous three-dimensional culture model (organotypic cultures). The epidermal growth factor receptor (EGFR) was chosen as target for an anti-CD3/anti-EGFR bimAb because it is overexpressed in many malignant epithelial lesions and only weakly expressed in the basal layers of normal squamous epithelium. Interestingly, in organotypic cultures, the pattern of expression of EGFR was similar to that observed in vivo. The ability of T cells retargeted by CD3/EGFR bimAb to lyse HPV-transformed cell lines was confirmed in monolayer cultures. In autologous organotypic cultures, an increase in apoptotic HPV+keratinocytes and a significant decrease in the thickness of HPV+organotypic cultures were observed when activated lymphocytes and bimAbs were added to the cultures, whereas organotypic cultures of normal keratinocytes were not significantly affected. These data were similar to those obtained in the allogeneic model. These results suggest the potential usefulness of CD3-EGFR bimAb-retargeted lymphocytes in immunotherapeutic protocols for malignant epithelial lesions.
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DOI：
--
发表时间：
1996-04
期刊：
The American journal of pathology
影响因子：
--
作者：
G. Sauter;T. Maeda;F. Waldman;R. Davis;B. Feuerstein
通讯作者：
G. Sauter;T. Maeda;F. Waldman;R. Davis;B. Feuerstein
由人乳头瘤病毒永生化的上皮细胞在器官型培养中具有癌前特征。
DOI：
--
发表时间：
1991
期刊：
The American journal of pathology
影响因子：
--
作者：
Blanton,RA;Perez-Reyes,N;Merrick,DT;McDougall,JK
通讯作者：
McDougall,JK
视黄酸和干扰素在肾癌细胞系中的相互作用。
DOI：
10.1089/10799900050151058
发表时间：
2000
期刊：
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.
影响因子：
--
作者：
Nanus,DM;Geng,Y;Shen,R;Lai,HK;Pfeffer,SR;Pfeffer,LM
通讯作者：
Pfeffer,LM
在器官型培养物中生长的人乳头瘤病毒 16 和 18 永生化上皮细胞中增殖和分化标记物的表达发生改变。
DOI：
--
发表时间：
1992
期刊：
The American journal of pathology
影响因子：
--
作者：
Merrick,DT;Blanton,RA;Gown,AM;McDougall,JK
通讯作者：
McDougall,JK
影响因子：
11.2
作者：
Coleman, S;Clayton, A;Tabi, Z
通讯作者：
Tabi, Z