Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma

Nat Commun. 2021 Mar 5;12(1):1453. doi: 10.1038/s41467-021-21774-4.


A major roadblock prohibiting effective cellular immunotherapy of pancreatic ductal adenocarcinoma (PDAC) is the lack of suitable tumor-specific antigens. To address this challenge, here we combine flow cytometry screenings, bioinformatic expression analyses and a cyclic immunofluorescence platform. We identify CLA, CD66c, CD318 and TSPAN8 as target candidates among 371 antigens and generate 32 CARs specific for these molecules. CAR T cell activity is evaluated in vitro based on target cell lysis, T cell activation and cytokine release. Promising constructs are evaluated in vivo. CAR T cells specific for CD66c, CD318 and TSPAN8 demonstrate efficacies ranging from stabilized disease to complete tumor eradication with CD318 followed by TSPAN8 being the most promising candidates for clinical translation based on functionality and predicted safety profiles. This study reveals potential target candidates for CAR T cell based immunotherapy of PDAC together with a functional set of CAR constructs specific for these molecules.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / therapy
  • Animals
  • Antigens, CD / metabolism*
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / therapy
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cytokines / metabolism
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Heterografts
  • Humans
  • Immunologic Factors
  • Immunotherapy / methods*
  • Lymphocyte Activation
  • Mice
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / therapy
  • T-Lymphocytes / immunology
  • Tetraspanins / genetics
  • Tetraspanins / metabolism*


  • Antigens, CD
  • Antigens, Neoplasm
  • CDCP1 protein, human
  • CEACAM6 protein, human
  • Cell Adhesion Molecules
  • Cytokines
  • GPI-Linked Proteins
  • Immunologic Factors
  • TSPAN8 protein, human
  • Tetraspanins

Supplementary concepts

  • Pancreatic Carcinoma