Abstract B091: Tandem chimeric antigne receptor T cell therapies for the treatment of pancreatic cancer
Priya Hays, Priya HaysAbstract
Background:
Chimeric antigen T cell therapy has entered into standard of care for hematologic malignancies such as B-ALL due to its robust efficacy. However, solid tumors such as pancreatic cancer pose challenges for CAR T cell therapies due to an immunosuppressive environment, antigen escape and tumor heterogeneity. As such, innovative CAR T cell constructs have been designed to overcome these challenges. Key strategies include targeting TAAs, addressing the TME, increasing persistence and constructing novel CAR T cell designs for improved infiltration. Tandem CARs or TanCARs are type of novel CAR T construct designed to target two antigens, mitigating antigen escape.
Methods:
PubMed and Google Scholar searches were conducted using "Pancreatic Cancer" AND "Tandem CARs" AND "Solid Tumors" AND "Challenges."
Results:
In one study on CAR T cells for treating solid tumors, tandem CARs targeting mesothelin and MUC16 overcame tumor heterogeneity by targeting ,multiple antigens one antigen at a time. A TanCAR construct was created that outperformed monospecific CAR T cells with SS1 and 4H11 targets had had best binding and activation in vitro. A TanCAR constructed to target both Meso and HER2 targets, creating an HM CAR T cell. The expression of HER2 and Meso in pancreatic cancer cell lines was evaluated by flow cytometry for evaluating and identifying targets for PDAC. ASPC-1 and SW-1990 cells were both found to be expressed at high levels, making them optimal target cells. HER2, Meso, and dual antigens on ASPC-1 cells were expressed at the rates of 77%, 92%, and 59%, respectively; for SW-1990 cells, the corresponding rates were 99%, 93%, and 93%. In mouse models, it was shown that tumor volume overload from each of the two single-target CAR-T cell treatment groups, whereas all mice in the HM CAR-T group survived. A Phase 1 trial is evaluating a tandem CAR for CLDN18.2 and NKG2D ligands (NKG2DLs) targets which are stress proteins often upregulated on tumor cells. Similarly, investigators have discovered other clinical or preclinical strategies combine targeting of two well-known pancreatic cancer antigens: CLDN18.2/PD-L1, MSLN/MUC16, MSLN/NKG2DL and EpCAM and ICAM-1 et al. By targeting two different antigens on one tandem CAR construct, this approach could reduce cancer likelihood by minimizing tumor evasion, increase the spectrum of tumor recognition and downregulate a single target.
Conclusions:
TanCARs have been found be an innovative and novel CAR T construct to address tumor heterogeneity and target TAAs in pancreatic cancer. Antigen escape is also prevented as well. Future studies may focus on the clinical applicability of these novel designs and constructs.
Citation Format:
Priya Hays, Priya Hays. Tandem chimeric antigne receptor T cell therapies for the treatment of pancreatic cancer [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr B091.