十一月 05, 2024

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新資金投入開發可異體移植的CAR-T免疫療法

今年美國有兩家新成立的公司Allogene Therapeutics及 Celularity分別籌資3億及2.5億美金要進行異體移植的CAR-T細胞治療技術的開發。

 

美國FDA目前所通過的兩個CAR-T療法都是透過自體細胞移植的方式進行,自體移植相對安全,但目前在製程仍較繁瑣且製造成本非常高。製程從病人血液中分離出T細胞開始,然後於體外進行細胞擴增及基因編輯,後續的純化、分析及QC檢測也是有相當多的流程要進行,要能順利進行一次製程就成功得到CAR-T細胞其實並是一件容易的事情,而且細胞在體外培養的過程中非常有可能因為一個環節的失誤而死亡。CAR-T是否能有機會變成一種隨手可取得的異體移植(Allogenic)療法呢? 相較於自體移植,異體移植成為的最重要的優勢就是方便且快速,病人不需等待漫長的細胞製程,醫療單位可以隨時取得現成可用的細胞來進行治療。下表為統整出來目前各生技藥廠正在開發的新一代CAR-T療法的計畫,從中可以看到目前僅有一間公司(Cellectis)正在進行異體移植的CAR-T開發計畫,目前已經進入臨床試驗一期,而另一個目前只有進行到臨床前試驗,其他CAR-T的都是以自體移植技術為主。

 

今年在美國有兩家新成立的公司Allogene Therapeutics及 Celularity分別籌資3億及2.5億美金要進行異體移植的CAR-T細胞治療技術的開發,其中Allogene和Cellectis開發的標的都是UCART19 (CD19-directed CAR-T cell therapy)。若異體移植的CAR-T能開發成功,在未來應該很有機會能夠成為具有商業規模的癌症治療方式。

 

Developer Therapy Description Target Indication Clinical stage
Autolus AUTO2 Dual-targeting autologous CAR-T cell therapy
directed at APRIL, a natural ligand for BCMA and
TACI and incorporating the RQR8 suicide switch
controlled by Rituxan (rituximab)
BCMA, TACI Multiple myeloma Phase 1/2
Cellectis, Servier
(Suresnes, France)
Pfizer
UCART19 Allogeneic CAR-T cells gene edited with TALENS
to disrupt the genes encoding the a-chain of
TRAC to reduce risk of graft versus host disease
and CD52 to confer Campath resistance
CD19 Adult relapsed/refractory
B-cell acute lymphoblastic
leukemia
Phase 1
Bellicum Pharmaceuticals
(Houston)
BPX-601 GoCAR-T cell product comprising autologous
T-cells containing a MyD88/CD40 activation
switch controlled by rimiducid, which amplifies
T-cell expansion via toll-like receptor and CD40
signaling
Prostate stem cell
antigen
Pancreatic cancer Phase 1
Celyad Cyad-101 Autologous T cells engineered to express NKG2D
receptor that binds stress ligands
Allows targeting
of multiple tumor
types
Seven refractory solid and
hematological cancers
Phase 1
Celularity, Sorrento
Therapeutics
(San Diego)
CD38 CAR-T Autologous CAR-T cell therapy based on adult
T cells to be followed by allogeneic CAR-T cell
therapies based on placental T cells and placental
natural killer cells modified to express a CD38-
directed CAR, with disruptions in the TCR and b2
microglobulin loci
CD38 Multiple myeloma Phase 1
CRISPR Therapeutics (Zug, Switzerland)CTX101 CD19-directed allogeneic CAR-T cell therapy with
CRISPR–Cas9-mediated disruption of the TRAC
and b2 microglobulin loci
CD19 B-cell malignancies Preclinical
Poseida Therapeutics
(San Diego)
P-BCMA-Allo1 Allogeneic CAR-T cells genetically modified with
the nonviral piggyBac DNA transposition system
and further modified with CRISPR-engineered
deletions of the TCR and b2 microglobulin genes
B-cell maturation
antigen (BCMA)
Multiple myeloma Preclinical
Ziopharm Oncology,
University of Texas MD
Anderson Cancer Center
(Houston)
CD19 third
generation CAR
with mbIL15
(P-O-C)
Autologous CAR-T cells genetically modified
with the Sleeping Beauty transposon system to
express CD19 and membrane-bound interleukin
15 (mbIL15)
CD19 Leukemia, lymphoma Preclinical
 

 參考資料:  NATURE BIOTECHNOLOGY VOLUME 36 NUMBER 5 MAY 2018 

 

今年在美國有兩家新成立的公司Allogene Therapeutics及 Celularity分別籌資3億及2.5億美金要進行異體移植的CAR-T細胞治療技術的開發,其中Allogene和Cellectis開發的標的都是UCART19 (CD19-directed CAR-T cell therapy)。若異體移植的CAR-T能開發成功,在未來應該很有機會能夠成為具有商業規模的癌症治療方式。

 

Allogene Therapeutics Pipeline

Allogene - PIPELINE

 

 Celularity Pipeline

Celularity Pipeline

 

參考資料:  NATURE BIOTECHNOLOGY VOLUME 36 NUMBER 5 MAY 2018

 

Last modified on 週六, 09 二月 2019 07:07