Near-infrared photoimmunotherapy is effective treatment for colorectal cancer in orthotopic nude-mouse models

PLoS One. 2020 Jun 18;15(6):e0234643. doi: 10.1371/journal.pone.0234643. eCollection 2020.

Abstract

Background: Photoimmunotherapy (PIT) employs the use of a near-infrared (NIR) laser to activate an antibody conjugated to a NIR-activatable dye to induce cancer cell death. PIT has shown to be effective in a number of studies, however, there are no data on its use in colorectal cancer in an orthotopic model.

Methods: Humanized anti-CEA antibody (M5A) was conjugated to NIR-activatable IRDye700DX (M5A-700). PIT was validated in vitro with a colon cancer cell-line, using a laser intensity of either 4 J/cm2, 8 J/cm2, or 16 J/cm2. Orthotopic colon cancer mouse models were established by surgical implantation of LS174T tumor fragments onto the cecum. M5A-700 was administered and PIT was performed 24 hours later using a 690 nm laser. Repeat PIT was performed after 7 days in one group. Control mice received laser treatment only.

Results: In vitro PIT demonstrated tumor cell death in a laser intensity dose-dependent fashion. In orthotopic models, control mice demonstrated persistent tumor growth. Mice that underwent PIT one time had tumor growth arrested for one week, after which re-growth occurred. The group that received repeated PIT exposure had persistent inhibition of tumor growth.

Conclusion: PIT arrests tumor growth in colon cancer orthotopic nude-mouse models. Repeated PIT arrests colon cancer growth for a longer period of time. PIT may be a useful therapy in the future as an adjunct to surgical resection or as primary therapy to suppress tumor progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Carcinogenesis / drug effects
  • Cell Line, Tumor
  • Colorectal Neoplasms / therapy*
  • Humans
  • Immunoconjugates / pharmacology*
  • Immunotherapy / methods*
  • Indoles / therapeutic use*
  • Mice
  • Mice, Nude
  • Organosilicon Compounds / therapeutic use*
  • Photosensitizing Agents / therapeutic use
  • Phototherapy / methods*
  • Receptors, Cell Surface / immunology*
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Substances

  • IRDye700DX N-hydroxysuccinimide ester
  • Immunoconjugates
  • Indoles
  • Organosilicon Compounds
  • Photosensitizing Agents
  • Receptors, Cell Surface
  • carcinoembryonic antigen binding protein, human

Associated data

  • figshare/10.6084/m9.figshare.12056157