Technical Name One step formulation of mPEGylated nanoparticles with humanized bispecific antibodies for cancer targeted therapy
Project Operator Kaohsiung medical university
Summary
Antibody (Ab)-conjugated mPEG-NPs display improved specific targeting and therapeutic efficacy toward tumors as compared to untargeted NPs. However, covalent chemical modification of Ab/ligands to PEG-NPs often leads to heterogeneous orientation of Ab/ligands and difficulty in obtaining a reproducible product. Here, we developed humanized bispecific antibodies (anti-mPEG Fab+anti-tumor marker scFv) (BsAbs) which can simultaneously bind the terminal methoxy end of mPEG and tumor markers. The BsAbs can non-covalent modify the terminal ends of mPEG on the surface of mPEG-NPs and confer tumor specificity to mPEG-NPs. We also anticipate that this one-step method can facilitate development of multiplex bsAbs possessing different tumor marker tropism, such as against EGFR, HER2, CD20, CD19, and CD22 to allow customized therapy depending on the tumor markers displayed on the cancer of each patient. The bsAbs of the invention will accelerate the clinical applications of PEG-NPs.
Scientific Breakthrough
因此本團隊的技術具有以下優點: 
1. 一個件簡單的混和步驟便可改變腫瘤專一性
2. 可依據不同病人的需求而修飾專屬的腫瘤專一性BsAb
3. 任何的mPEG-NPs皆可被BsAb修飾
4. 人類化的雙專一性抗體可降低免疫反應
5. 修飾後抗體方向性一致
6. 奈米的結構不因BsAb修飾改變。
Industrial Applicability
臨床功效及產業發展-
1. 增加奈米藥物之腫瘤標靶性,提升臨床治療效果:調整雙功能抗體修飾量可提升藥物累積於腫瘤細胞內的情形,而增加藥物治療效率。
2.〝one-step formulation〞修飾抗體方式,增加標靶奈米藥物穩定度,降低生產成本:雙功能抗體與PLD只需要使用前均勻混合後即可完成修飾,不需要特殊條件,臨床使用前才混和修飾,可提升藥物穩定度,簡易快速,且降低過程中浪費成本。
3. anti-PEG雙功能抗體專利可不斷延伸:雙功能抗體也不只結合PLD,也可以結合不同任何有修飾mPEG的奈米藥物。另外,此技術不只有mPEG×HER2,還可以應用於不同marker,使奈米具有標靶性,甚至應用非腫瘤領域,未來將可以擴展到各疾病領域。
4. PLD市場不斷成長,臨床需求增加:Grand View Research, Inc分析PLD的2015全球市場有8.14億美金,而預估於2024全球市場可高達近14億美金,且年均複合增長率(CAGR)可以達6.2%。
5. 與生產PLD廠商合作,共同開發出標靶性奈米:台灣於Liposome formulation技術發展相當成功,有廠商甚至具有全球市場,因此若成功開發anti-PEG雙功能抗體,將可加值原本奈米藥物價值。
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