Overview
(iPS-T™: iPSC-derived T cell)
Young T Cells
Rejuvenated and highly cytotoxic
to target tumor cells.
Large Amount
Easy to treat patients
with few tumor specific T cells.
A large amount of young T cells break through immuno-suppressive environment
and completely eliminate tumors.
Multiple Times
Autologous iPS-T can be safely infused multiple times without auto-immune response.
For Many Types of Cancers
Targeting many types of cancer antigens
with iPS-T utilizing cancer vaccines
Characteristics
iPS-T Eliminates Tumor Cells while Proliferating
Exhausted parental T cells
iPS-T
iPS-T Demonstrates Specific Cytotoxicity against Tumor Cells
iPS-Ts only attack the targeted cancer cells.
Red ： iPS-T specific to antigen X
Green： Tumor cells NOT expressing antigen X
(iPS-T patrols but does not attack
the tumor cells)
Red ： iPS-T specific to antigen X
Green： Tumor cells expressing antigen X
(iPS-T attacks and eliminates
the tumor cells)
Cell Stem Cell | (2018) 23:1–9 | https://doi.org/10.1016/j.stem.2018.10.005
iPS-T is CD8α+β+ T cells
- iPS-T expresses CD8α+β+.
- iPS-T has high avidity to target antigens (adaptive immunity) while CD8α+α+ T cells have low avidity to them (innate immunity).
CD8αβ
Strong TCR signals
for antigen specific cytotoxicity
CD8αα
Insufficient TCR signals
for antigen specific cytotoxicity
Cell Stem Cell | (2018) 23:1–9 | https://doi.org/10.1016/j.stem.2018.10.005
iPS-T Regains Naive T Cell Phenotype
- Memory T cells play a key role in immune surveillance and long-term immunity.
- It is reported clinical efficacy of immune checkpoint inhibitors, or CAR-T has a strong positive correlation with the proportion of memory/naive T cells in patients’ body.
iPS-T is Proliferative as Naïve T cells
- iPS-T has longer telomere than parental T cells.
Elongation of iPS-T‘s telomere
Correlation between the efficacy of T cell therapy
and the telomere length is reported.
Nat Rev Cancer | (2008) 8: 299–308 | https://doi.org/10.1038/nrc2355
iPS-T‘s high ability of proliferation
Exhausted T cells do not proliferate well,
while iPS-T shows massive growth
as naïve T cells do.
iPS-T Reduces Expression of Exhaustion Markers
- iPS-T has no/low expression of exhaustion markers unlike patients’ exhausted T cells.
Patient’s exhausted T cell
When immune checkpoint receptors on
T cells are activated, cytotoxic responses of
T cells are suppressed.
iPS-T
As iPS-T cells express no/less
immune
check points receptors,
potent cytotoxic responses
against tumor cells are regained.
Auto-iPS-T Can be Injected Multiple Times in a Large Amount
- A recent case report of the CAR-T trial suggests multiple infusions of a large amount of
T cells are highly effective to cure patients. - Autologous iPS-T is safely infused multiple times, which may lead to durable response.
NATURE COMMUNICATIONS | (2020) 11:3549 https://doi.org/10.1038/s41467-020-17175-8
Pipeline
Peptide Vaccine (specific to antigen X)
- Phase 1 & 2 clinical trials complete at National Cancer Center Japan.
- Proven to be safe and tolerated.
- Induced antigen X specific killer T cells in tumor tissues and peripheral blood (Immunologically cold tumor became hot).
Pre-vaccine
Post-vaccine
Brown dots: CD8+ T cells infiltrating
into tumor tissues
Photo：National Cancer Center Japan
Thyas Can Produce Clinical Scale iPS-T
- Regenerated T cells (iPS-T) from tumor specific patient’s T cells
- Thyas can produce 3x10e9 (3 billion cells) iPS-Ts (clinical scale production).
T cell-derived iPSC
Rejuvenated Tcells (iPS-T)
（Grown like activated T cells：T-Blast）