CT041 CAR T cell therapy for Claudin18.2-positive metastatic pancreatic cancer

Abstract

Pancreatic cancer lacks effective therapy. Here, we reported two metastatic pancreatic cancer patients administrated with Claudin 18.2 (CLDN 18.2) CART therapy after the failure of standard therapy (NCT04581473 and NCT03874897). In case 1, with CLDN 18.2 expression of 2+, 70%, 250 × 10⁶ cells were infused after lymphodepletion. Grade 1 cytokine release syndrome (CRS) occurred on d1 which was later controlled by tocilizumab. Partial response (PR) was achieved according to RECIST v1.1, with great shrinkage of lung metastasis. An increasing CD8+ T cell and Treg cells and declining CD4+ T cell and B cell were observed. In case 2, IHC result of ClDN18.2 showed 3+, 60%. 250 × 10⁶ CLDN18.2 CART cells were subsequently administered. Patient experienced grade 2 CRS, which was controlled with tocilizumab. Target lesions of lung metastasis further achieved complete response. Similar increasing CD8+ T cell and Treg cell was detected from peripheral blood. Elevating IL-8 and declining TGF-β1 were also observed. The tumor is still under well control until the last follow-up on July 18, 2023.

Fig. 1

Radiological evaluation of lung lesions in case 1 (A) and case 2 (B). Red arrow in A showed the progressed lesion; red arrow in B indicated the target lesion. * indicated the primary lesion

Fig. 2

Dynamic changes of A CLDN18.2 CAR copy numbers, B cytokine levels and C peripheral blood lymphocyte subsets according to the time after CT041 infusion