title: Enhanced delivery of T cells to tumor after chemotherapy using membrane-anchored, apoptosis-targeted peptide.
abstract: Chemotherapy-induced apoptosis of tumor cells enhances the antigen presentation and sensitizes tumor cells to T cell-mediated cytotoxicity. Here we harnessed the apoptosis of tumor cells as a homing signal for the delivery of T cells to tumor. Jurkat T cells were anchored with ApoPep-1, an apoptosis-targeted peptide ligand, using the biocompatible anchor for membrane (BAM), an oleyl acid derivative. The ApoPep-1-BAM conjugate was efficiently anchored to cell membrane, while little anchoring was obtained with ApoPep-1 alone. The retention period of the ApoPep-1-BAM conjugate on cell membrane was approximately 80 and 40 min in the absence and presence of serum, respectively. ApoPep-1 was resistant to degradation in serum until 2h. The apoptosis-targeted T cells that were anchored with the ApoPep-1-BAM preferentially bound to apoptotic tumor cells over living cells. When intravenously injected into tumor-bearing mice, the number of apoptosis-targeted T cells and in vivo fluorescence signals by the homing of the cells to doxorubicin-treated tumor were higher than those of untargeted T cells. Accumulation of apoptosis-targeted T cells at other organs such as liver was not detected. These results suggest that the chemotherapy-induced apoptosis and subsequent enhancement of T cell delivery to tumor by the membrane anchoring of the apoptosis-targeted peptide could be a novel strategy for cancer immunotherapy.
authors: Department of Biochemistry and Cell Biology, School of Medicine, and Cell & Matrix Research Institute, Kyungpook National University, Daegu, Republic of Korea.
authors: Xiaofeng
authors: X
authors: He
authors: Napolean
authors: N
authors: Bonaparte
authors: Soyoun
authors: S
authors: Kim
authors: Bodhraj
authors: B
authors: Acharya
authors: Ji-Young
authors: JY
authors: Lee
authors: Lianhua
authors: L
authors: Chi
authors: Hyoung-Joo
authors: HJ
authors: Lee
authors: Young-Ki
authors: YK
authors: Paik
authors: Pyong-Gon
authors: PG
authors: Moon
authors: Moon-Chang
authors: MC
authors: Baek
authors: Eun-Kyu
authors: EK
authors: Lee
authors: Jong-Ho
authors: JH
authors: Kim
authors: In-San
authors: IS
authors: Kim
authors: Byung-Heon
authors: BH
authors: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis; D001672:Biocompatible Materials / Q000737:chemistry; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006801:Humans; D016219:Immunotherapy, Adoptive; D051379:Mice; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D009842:Oligopeptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D001672:Biocompatible Materials; D009842:Oligopeptides; C578342:cysteinyl-glutaminyl-arginyl-prolyl-prolyl-arginine; D011092:Polyethylene Glycols; D016650:Fluorescein-5-isothiocyanate