雙特異性anti-CD3×anti-CD155抗體介導t細胞免疫治療人類血液病惡性腫瘤

2023年5月，首都醫(yī)科大學附屬北京同仁醫(yī)院頭頸部分子診斷病理學北京市重點實驗室病理科;首都醫(yī)科大學附屬中日友好醫(yī)院婦產(chǎn)科;首都醫(yī)科大學附屬北京世紀壇醫(yī)院生物醫(yī)學創(chuàng)新中心;首都醫(yī)科大學;北京大學醫(yī)學部基礎醫(yī)學院(Department of Pathology, Beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730 ,China；Department of Gynecology and Obstetrics, China-Japan Friendship Hospital, Capital Medical University, Beijing 100029, China；Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China；Department of Clinical Laboratory Medicine, Beijing Shijitan Hospital,Capital Medical University,   Beijing 100038, China；College of Basic Medical Science, Peking University Health Science Center, Beijing 100191, China) Honggang Liu老師研究團隊在《Investigational New Drugs》上發(fā)表論文：

“Bispecific anti-CD3×anti-CD155 antibody mediates T-cell immunotherapy in human haematologic malignancies”

“雙特異性anti-CD3×anti-CD155抗體介導t細胞免疫治療人類血液病惡性腫瘤”

Abstract：

T cells are important components in the cell-mediated antitumour response. In recent years, bispecific antibodies (Bi-Abs) have become promising treatments because of their ability to recruit T cells that kill tumours. Here, we demonstrate that CD155 is expressed in a wide range of human haematologic tumours and report on the ability of the bispecific antibody anti-CD3 x anti-CD155 (CD155Bi-Ab) to activate T cells targeting malignant haematologic cells. The specific cytolytic effect of T cells armed with CD155Bi-Ab was evaluated by quantitative luciferase assay, and the results showed that the cytolytic effect of these cells was accompanied by an increase in the level of the cell-killing mediator perforin. Moreover, compared with their unarmed T-cell counterparts, CD155Bi-Ab-armed T cells induced significant cytotoxicity in CD155-positive haematologic tumour cells, as indicated by lactate dehydrogenase assays, and these results were accompanied by increased granzyme B secretion. Furthermore, CD155Bi-Ab-armed T cells produced more T-cell-derived cytokines, including TNF-α, IFN-γ, and IL-2. In conclusion, CD155Bi-Ab enhances the ability of T cells to kill haematologic tumour cells, and therefore, CD155 may serve as a novel target for immunotherapy against haematologic malignancies.

摘要：

T細胞是細胞介導的抗腫瘤反應的重要組成部分。近年來，雙特異性抗體(Bi-Abs)已成為有希望的治療方法，因為它們能夠招募殺死腫瘤的T細胞。在這里，科研人員證明CD155在廣泛的人類血液腫瘤中表達，并報道了雙特異性抗體抗cd3 x抗CD155 (CD155Bi-Ab)激活靶向惡性血液細胞的T細胞的能力。用熒光素酶定量測定方法評價了攜帶CD155Bi-Ab的T細胞的特異性細胞溶解作用，結(jié)果表明，這些細胞的細胞溶解作用伴隨著細胞殺傷介質(zhì)穿孔素水平的增加。此外，乳酸脫氫酶檢測表明，與未攜帶cd155bi - ab的T細胞相比，攜帶cd155bi - ab的T細胞對cd155陽性的血液學腫瘤細胞具有顯著的細胞毒性，并且這些結(jié)果伴隨著顆粒酶B分泌的增加。此外，cd155bi - ab武裝的T細胞產(chǎn)生更多的T細胞源性細胞因子，包括TNF-α， IFN-γ和IL-2。總之，CD155Bi-Ab增強了T細胞殺死血液腫瘤細胞的能力，因此，CD155可能作為免疫治療血液惡性腫瘤的新靶點。

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