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Near-Infrared Photoimmunotherapy Therapy (PIT)

A new antibody conjugate system that enables highly specific cancer cell killing by direct contact to the cell surface.

Aspyrian Therapeutics has secured the exclusive license to a new antibody drug conjugate (ADC) technology platform from the National Cancer Institute (NCI): near-infrared photoimmunotherapy (PIT). Aspyrian’s mission is to leverage the potential of the PIT platform by developing a pipeline of proprietary and partnered products. 

PIT was developed by Dr. H. Kobayashi and Dr. P. L. Choyke, the scientific heads of the Molecular Imaging Program at the National Cancer Institute (NCI) and described in Nature Medicine (1).  

Video Describing the Technology

 

Photoimmunotherapy (PIT) is based on three components:

  1. An antibody that binds surface antigens (e.g. cancer) for cell-selective targeting.
  2. The near-infrared IR700DX dye conjugated to the antibody with stable linkers.
  3. Near-infrared light dosimetry to activate locally the Ab/IR700DX dye conjugate when bound to surface membranes. 

PIT induces rapid cell killing by localized disruption of the cell membrane only after antibody binding to the surface of cells, and after tumor localized activation of the dye with non-ionizing NIR light. Importantly, unbound Ab/IR700 conjugates, or the free IR700DX dye, do not elicit any phototoxicity upon NIR irradiation. The combination of selective binding to surface antigens and organ localized NIR activation permits highly efficacious disease-specific ablation while preserving organ function.

VIDEO: Real-time observation of Tra-IR700 mediated phototoxic cell death after cell surface binding.

VIDEO: Real-time observation of Tra-IR700 mediated phototoxic cell death after receptor internalization.

VIDEO: Target specific phototoxicity in response to Tra-IR700 mediated photoimmunotherapy in vitro.

References

  1. Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules. Mitsunaga M, Ogawa M, Kosaka N, Rosenblum LT, Choyke PL, Kobayashi H. Nat Med. 2011 Nov 6; 17 (12): 1685-91.
  2. Near-infrared Theranostic Photoimmunotherapy (PIT): Repeated Exposure of Light Enhances the Effect of Immunoconjugate. Mitsunaga M, Nakajima T, Sano K, Choyke PL, Kobayashi H. Bioconjug Chem. 2012 Mar 21; 23(3): 604-9.