After biopsy and PET-CT scan, a 58-year-old woman was diagnosed with pancreatic cancer with lung and lymph nodes metastasis. First-line nab-paclitaxel plus gemcitabine and second-line irinotecan-liposome plus 5-flurouracil were failed before she was enrolled in CT041 phase 1 clinical trial (Additional file 4: Figure S4), after confirming 2+, 70% expressing of CLDN18.2 (Additional file 1: Figure S1).

One cycle of FOLFIRI was bridged on August 26, 2021. After lymphodepletion consisting of fludarabine, cyclophosphamide, and nab‐paclitaxel, a CT041 dose of 250 × 106 cells was infused on September 22 (Additional file 2: Figure S2; Additional file 6: methods). Grade 1 cytokine release syndrome (CRS) occurred on D1 and upgraded to grade 2 on D3, until the administration of tocilizumab (Additional file 3: Figure S3). Partial response (PR) was achieved according to RECIST v1.1 (Fig. 1A), and liver lesion progressed on March 8, 2022, and the patient died due to disease progression on July 23, 2022.

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

The peripheral blood CLDN18.2 CAR copy reached peak on D7 and dropped below the limit of quantification after week 4. Fluorescence-activated cell sorting (FACS) showed a decrease in CD4+ T cells and B cells and an increase in CD8+ T cells and Treg cells. CD8+ T cells occupied nearly half of the total lymphocytes in the next 3 months. In contrast, CD4+ T cells remained at lower levels, but gradually increased for 3 months after CT041 infusion (Additional file 5: Table S1). Cytokine analysis showed a significant increase of IL-6 level since D3 and a significant reduction by week 4, contradictory to TGF-β1 and Treg (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