公开(公告)号：WO2022066768A1

公开(公告)日：2022-03-31

申请号：PCT/US2021/051551

申请日：2021-09-22

Applicant: VIRGINIA TECH INTELLECTUAL PROPERTIES, INC.

Inventor： DAVALOS, Rafael, V. ,  ALLEN, Irving, C. ,  VERBRIDGE, Scott, S. ,  ALINEZHADBALALAMI, Nastaran

IPC: A61K35/17 ,  A61N1/32 ,  A61P35/00

Abstract: Expansion of cytotoxic T lymphocytes (CTLs) is a crucial step in almost all cancer immunotherapeutic methods. Current techniques for expansion of tumor-reactive CTLs present major limitations. The present invention comprises a novel method to effectively produce and expand tumor-activated CTLs using high-voltage pulsed electric fields. Tumor cells were subjected to high-frequency irreversible electroporation (HFIRE) with various electric field magnitudes and pulse widths, or irreversible electroporation (IRE). The treated tumor cells were subsequently cocultured with CD 8+ cytotoxic T cells along with antigen-presenting cells. Tumor- activated CTLs can be produced and expanded when exposed to treated tumor cells. The activated CTLs produced with the present invention could be used for clinical applications with the goal of targeting and eliminating tumors.

公开(公告)号：WO2015175570A1

公开(公告)日：2015-11-19

申请号：PCT/US2015/030429

申请日：2015-05-12

Applicant: VIRGINIA TECH INTELLECTUAL PROPERTIES, INC. ,  SANO, Michael, B. ,  ARENA, Christopher, B. ,  VERBRIDGE, Scott, S. ,  DAVALOS, Rafael, V.

Inventor： SANO, Michael, B. ,  ARENA, Christopher, B. ,  VERBRIDGE, Scott, S. ,  DAVALOS, Rafael, V.

IPC: C12N5/00 ,  C12N5/02

CPC classification number: A61N1/327 ,  A61B18/1206 ,  A61B18/1477 ,  A61B90/37 ,  A61B2017/00172 ,  A61B2018/00577 ,  A61B2018/126 ,  A61B2018/143 ,  A61N1/06 ,  A61N1/08 ,  A61N1/40

Abstract: A system and method for selectively treating aberrant cells such as cancer cells through administration of a train of electrical pulses is described. The pulse length and delay between successive pulses is optimized to produce effects on intracellular membrane potentials. Therapies based on the system and method produce two treatment zones: an ablation zone surrounding the electrodes within which aberrant cells are non- selectively killed and a selective treatment zone surrounding the ablation zone within which target cells are selectively killed through effects on intracellular membrane potentials. As a result, infiltrating tumor cells within a tumor margin can be effectively treated while sparing healthy tissue. The system and method are useful for treating various cancers in which solid tumors form and have a chance of recurrence from microscopic disease surrounding the tumor.

Abstract translation: 描述了通过施加一系列电脉冲来选择性地治疗异常细胞例如癌细胞的系统和方法。 优化连续脉冲之间的脉冲长度和延迟，以产生对细胞内膜电位的影响。 基于系统和方法的治疗产生两个治疗区：围绕电极的消融区，其中异常细胞被非选择性杀死，围绕消融区的选择性治疗区，通过对细胞内膜电位的影响，靶细胞被选择性地杀死。 因此，可以有效地治疗肿瘤边缘内的浸润肿瘤细胞，同时节省健康组织。 该系统和方法可用于治疗各种癌症，其中实体瘤形成并有机会从肿瘤周围的微观疾病复发。