Photochemical internalization of CD133-targeting immunotoxins efficiently depletes sarcoma cells with stem-like properties and reduces tumorigenicity

Biochim Biophys Acta. 2013 Aug;1830(8):4235-43. doi: 10.1016/j.bbagen.2013.04.033. Epub 2013 May 2.


Background: The normal stem cell marker CD133 is also a putative marker of cancer stem cells (CSCs) in different types of cancers. Hence, a major challenge when targeting CD133-expressing CSCs is to prevent depletion of the normal stem cell pool. We hypothesized that the site-specific and light-controlled drug delivery method photochemical internalization (PCI) may have the potential to enhance selectivity and endosomal escape of CD133-targeting immunotoxins in stem-like sarcoma cells.

Methods: We have used a sarcoma model, SW872 cells isolated from xenografts harboring CSCs within a ~2% CD133(high) subpopulation to investigate the potential of PCI of CD133-targeting toxin as a novel strategy to kill CSCs. Model immunotoxins were generated by binding the ribosome-inactivating protein toxin saporin to each of the monoclonal antibodies CD133/1 (AC133) or CD133/2 (293C), specific for individual CD133-epitopes. Cellular targeting, intracellular co-localization with the PCI photosensitizer, disulfonated meso-tetraphenylchlorin (TPCS2a), and cytotoxic efficacy of PCI of the CD133-targeting toxins were evaluated.

Results: PCI of CD133-saporin efficiently targets CD133-expressing SW872 and HT1080 sarcoma cells and results in loss of cell viability. Following sub-toxic treatment, surviving SW872 cells, depleted of the CD133-expressing population, display reduced proliferative capacity and attenuated CSC properties, such as reduced colony-forming ability and tumorigenicity.

Conclusion: Here we present a proof-of-concept study, where PCI enables light-triggered delivery of CD133-targeting antibody-drug conjugates, resulting in decreased sarcoma tumor-initiating capacity.

General significance: PCI of CD133-targeting toxins may be used as a minimal invasive strategy in the treatment of sarcomas, and potentially as a therapeutic for other solid tumors expressing CD133.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Animals
  • Antigens, CD / immunology
  • Cell Line, Tumor
  • Drug Delivery Systems
  • Glycoproteins / antagonists & inhibitors*
  • Glycoproteins / immunology
  • Humans
  • Immunotoxins / administration & dosage*
  • Mice
  • Mice, SCID
  • Neoplastic Stem Cells / drug effects*
  • Peptides / antagonists & inhibitors*
  • Peptides / immunology
  • Photochemistry
  • Photosensitizing Agents / administration & dosage*
  • Sarcoma / drug therapy*
  • Sarcoma / pathology
  • Xenograft Model Antitumor Assays


  • AC133 Antigen
  • Antigens, CD
  • Glycoproteins
  • Immunotoxins
  • PROM1 protein, human
  • Peptides
  • Photosensitizing Agents
  • Prom1 protein, mouse