Genetic modification of lymphocytes by retrovirus-based vectors

Adoptive Immunotherapy for Cancer or Viruses

“…Also, in 1990, two girls suffering from adenosine deaminase severe combined immunodeficiency (ADA SCID) were treated by T lymphocytes transduced with a gammaretrovirus expressing the ADA gene, which led to the reconstitution of the patient’s immune system with those gene-corrected T cells (82). Since then, retroviral vectors have been the major tools for permanent transgene expression, and have been widely used as vehicles to deliver genes into different type of cells for gene therapy, including T lymphocytes (83, 84). Hematopoietic stem cells (HSCs), which have the potential to self-renew and differentiate into all blood lineages, were initially thought to be the most desirable targets for retroviral gene modification for the treatment of genetic disorders and other diseases (85-91).…”

“…Lentiviruses are distinct members of the retroviruses family. Lentiviral vectors have been constructed from several types of lentiviruses, but the most commonly used is the human immunodeficiency virus (HIV), because its molecular biology has been extensively studied (83, 105). …”

Adoptitive immunotherapy with genetically engineered T lymphocytes modified to express chimeric antigen receptors

“…Привлекательны как высокая эффективность, так и большой спектр доступных клеточных линий -про-дюсеров вирусных частиц. Длительный срок наблюде-ния за пациентами, получившими терапию Т-лимфо-цитами, модифицированными гамма-ретровирусами, продемонстрировал безопасность метода [37,38]. В от-личие от ретровирусной трансдукции гемопоэтических стволовых клеток, при трансдукции Т-лимфоцитов не было зарегистрировано ни одного случая злокачест-венной трансформации.…”

Manufacture of tumor- and virus-specific T lymphocytes for adoptive cell therapies

“…The rationale and strategy of TCR and CAR design and their evolution have been comprehensively reviewed elsewhere. 36,37 …”