Technology

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)