Table 3 Milestones of gene and cell therapies, as well as notable technologies. Oligonucleotides therapies are not included in this table
From: Current strategies employed in the manipulation of gene expression for clinical purposes
Year | Notable technology | Gene therapy | Cell therapy |
|---|---|---|---|
1962 | |||
1968 | Rogers and Pfuderer demonstrated virus mediated gene transfer [180] | ||
1972 | Literature outlined the potential and concerns of gene therapy [276] | ||
1976 | T cell growth factor interleukin 2 discovered [277] | ||
1982 | |||
1983 | Identification of human T cell antigen receptor [279,280,281] | ||
1984 | RVV transduced mammalian cells in vitro [282] | ||
1989 | AV approved for clinical trial [283] | Concept of CAR-T appeared [284] | |
1990 | First successful ex vivo gene therapy performed on an ADA-SCID patient [181] | ||
1993 | 1st gen CAR-T cells developed [285] | ||
1996 | 1st gen LVVs created [286], ZFN gene editing system available [253] | ||
1997 | SB transposon system designed for human cells [287] | FDA approved 1st anti-cancer monoclonal antibody Rituxan for NHL [288] | |
1999 | A patient died due to immune response triggered by in vivo AV-based therapy [289] | ||
2000 | 4-component LNP reported [235] | Some SCID-X1 patients received ex vivo, RVV-based gene therapy [290] | |
2003 | First approved LVV use in a phase 1 trial (ex vivo, for HIV control) [291] | Reports of RVV related tumorigenesis in two patients after gene therapy for SCID-X1 [292] | |
2005 | New RNA modification to reduce immunogenicity developed [166], PB transposon system applied to mammalian cells [114] | ||
2006 | TCR therapy applied to melanoma [293] | ||
2007 | First IND for CD19 CAR-T [294] | ||
2009 | Reports of eye disease treated in vivo with AAV-based vector [295] | ||
2010 | TALEN gene editing system available [268] | ||
2011 | |||
2012 | EMA approved Glybera (withdrawn in 2017 for market reason) [302] | ||
2015 | First BCMA CAR-T clinical trial [303] | ||
2016 | CRISPR/Cas9 applied to T cell engineering [304] | EMA approved Strimvelis [305] | |
2017 | FDA approved Luxturna [306] | FDA approved first cell therapies Yescarta [307]and Kymriah [308] | |
2018 | Multiple CRISPR clinical trials combined CAR-T and PD-1 KO for cancer immunotherapies [304] | ||
2019 | |||
2020 | FDA approved Tecartus [311] | ||
2021 | |||
2022 | FDA approved Carvykti [314] |