Cellectis another spot-type CAR-T announces positive preclinical data for the treatment of solid tumors

Article source: Medical Rubik's Cube Pro

Author: Bai Lu

On November 12, at the annual meeting of the Society for Cancer Immunotherapy (SITC), Cellectis announced the first allogeneic CAR-T cell candidate product UCARTMESO targeting Mesothelin (MSLN) for the treatment of pancreatic cancer and mesothelioma.

MSLN is a potential target of CAR-T cell therapy for solid tumors because it is highly uniformly expressed in mesothelioma and pancreatic cancer

Source: Cellectis official website

The UCARTMESO product candidate is edited by mRNA encoded with TALEN technology to destroy the TRAC, CD52 and TGFBR2 genes, and transduced in vitro with recombinant lentiviral vectors (rLV) to express the second generation of CAR targeting MSLN

1) TCRα gene knockout minimizes the occurrence of GvHD;

2) CD52 gene knockout can improve the durability of UCARTMESO in the presence of alemtuzumab (an anti-CD52 monoclonal antibody that can be used for clearing leaching);

3) TGFβR2 gene knockout protects UCARTMESO from the inhibitory effect of TGFβ

Source: Cellectis official website

Due to the knockout of TGFBR2 (TGFβ receptor) gene, UCARTMESO can restore IL2Rα up-regulation when activated in vitro, even in a medium rich in TGFB1, which contributes to the immunosuppressive microenvironment in tumors

Source: Cellectis official website

Preclinical data show that UCARTMESO has strong activity on MSLN expressing cell lines in vitro and in vivo, and in vivo activity in mouse models of pancreatic cancer and pleural mesothelioma

Source: Cellectis official website

Specifically, in vitro experiments showed that TGFβR2 knockout MESOCAR-T cells showed in vitro cytotoxic activity against H226 cells (a mesothelioma cell line that expresses MSLN and can produce TGFβ)

An immunodeficiency mesothelioma model mouse was used to evaluate the in vivo activity of TGFβR2 knockout MESOCAR-T cells

1) Tumor regression (and increased survival rate) was observed in all mice treated with CAR-T

2) At the end of the study (day 70), tumors were almost undetectable at the therapeutic dose of 3x106 CAR-T cells

The release of Cellectis' data comes at a difficult time for spot CAR-T therapy

However, Allogene's dilemma gradually spread to Cellectis, because the latter created the TALEN gene editing technology used to make ALLO-501A

Note: The original text has been deleted

Reference materials:

1# UCARTMESO: Mesothelin (MSLN) targeting allogeneic CAR-T cells engineered to overcome tumorimmunosuppressive microenvironment.

2#Cellectis Presents First Preclinical Data on UCARTMESO,an Allogeneic CAR-T Cell Product Candidate Targeting Mesothelin to Treat SolidTumors at the Annual Meeting of the Society for Immunotherapy of Cancer (Source: Cellectis official website)

3# SITC: Cellectis' off-the-shelf CAR-T for pancreatic cancer and mesothelioma shows activity in mice (Source: FIERCE Biotech)