5th Generation Universal Strengthened Chimeric Antigen Receptor T-Cell Immunotherapy

New Generation of CAR-T:

  • Integration of suicide gene, to limit the risk of unwanted result caused by long term stay of genetically modified T cell in the system.
  • Precision regulation of cytokine release and activation to avoid “cytokine storm”
  • Universal CAR-T to overcome the the shortcoming of common CAR:
    • highly individualized.
    • unsuitable for cGMP management.
    • high cost.

poor condition of  T cells from the patient may not fit for genetic maneuvers.

Major Breakthroughs in USCAR-T Technology

A.    Non Viral Trans-infection

  • One of severe side effect of CAR-T therapy, Cerebral edema, which may be contributed by vial construct or viral preparation method. Non-viral trans-infection method can avoid this risk.
  • Pinpoint insertion to avoid random viral insertion which may cause off-target effect.
  • Variety of non-viral methods can be selected according to construct.

B. Universal CAR with Immune Knockout T Cell

  • Low cell count and vitality of patient’s autologous T cells are often with function damage or loss, may not ideal for genetic maneuver and ex vivo expansion.
  • Individualized therapy is highly expensive.  The time-consuming procedure may delay treatment.
  • Lab scaled preparation can hardly satisfy the needs of industrial scaled, ready-made cell manufacture.

 

C. Inserting“Suicidal Gene”and“Molecular Switch ” 

  • To resolve the problems of:
    • Cytokine Release Syndrome

    (CRS) or “cytokine storm”

    • Potential risk from the long

    term stay of transgenic T cell’s

    • Cancer risk from the mutation of inserted gene

Comparison of Old and New CAR-T Technology

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USCAR-T non-viral method with same level of trans-infection rate

  1. Lower cost at least 80%
  2. The whole procedure shortens 9 months of treatment time

USCAR-T each treatment only cost $4000 according to Cellectis，which is 1/100 of Norvatis’CD19 （Kymriah™）procedure。

USCAR-T deactivates immune inhibitory genes like TGF-beta receptor，PD1，destroys the micro environment of solid tumors so to strengthen T cell function in treating liver matastases of colon cancer and pancreatic cancer or other solid tumor. The market is estimated at 100 billions.

CAR co-express IL-12 or  IL-15 can also greatly increase CAR-T killing function.