Near infrared photoimmunotherapy targeting bladder cancer with a canine anti-epidermal growth factor receptor (EGFR) antibody

Abstract

Anti-epidermal growth factor receptor (EGFR) antibody therapy is used in EGFR expressing cancers including lung, colon, head and neck, and bladder cancers, however results have been modest. Near infrared photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate which is activated by NIR light. NIR-PIT is in clinical trials in patients with recurrent head and neck cancers using cetuximab-IR700 as the conjugate. However, its use has otherwise been restricted to mouse models. This is an effort to explore larger animal models with NIR-PIT. We describe the use of a recombinant canine anti-EGFR monoclonal antibody (mAb), can225IgG, conjugated to the photo-absorber, IR700DX, in three EGFR expressing canine transitional cell carcinoma (TCC) cell lines as a prelude to possible canine clinical studies. Can225-IR700 conjugate showed specific binding and cell-specific killing after NIR-PIT on EGFR expressing cells in vitro. In the in vivo study, can225-IR700 conjugate demonstrated accumulation of the fluorescent conjugate with high tumor-to-background ratio. Tumor-bearing mice were separated into 4 groups: (1) no treatment; (2) 100 µg of can225-IR700 i.v. only; (3) NIR light exposure only; (4) 100 µg of can225-IR700 i.v., NIR light exposure. Tumor growth was significantly inhibited by NIR-PIT treatment compared with the other groups (p < 0.001), and significantly prolonged survival was achieved (p < 0.001 vs. other groups) in the treatment groups. In conclusion, NIR-PIT with can225-IR700 is a promising treatment for canine EGFR-expressing cancers, including invasive transitional cell carcinoma in pet dogs, that could provide a pathway to translation to humans.

RNAseq expression patterns of canine invasive urothelial carcinoma reveal two distinct tumor clusters and shared regions of dysregulation with human bladder tumors

“…Clinical EGFR inhibitor trials are currently underway in dogs [3,58]. We did not observe clustering based on luminal or basal signatures.…”

Near Infrared Light Triggered Photo/Immuno-Therapy Toward Cancers

“…An example is polydopamine coating improved the absorption capacity of gold nanoparticles, reported by Nam et al (2019). It has been reported that IR700-formed APC showed a biodistribution similar to non-conjugated parental antibodies, once injected intravenously, the APC will have a sufficient accumulation in the tumors (Mitsunaga et al, 2011;Nagaya et al, 2018). However, it is still challenging for the nanomaterials-based phototherapy that the recognization and clearance of the nanomaterials by the cells in liver, spleen and other parts of the reticuloendothelial system (RES) may reduce the concentration of the therapeutics in the tumor sites.…”

Molecular targets for anticancer therapies in companion animals and humans: what can we learn from each other?

“…These data show promising effects and follow-up studies are warranted. In another recent study, near-infrared photoimmunotherapy was used to target EGFR in canine invasive TCC cell lines 50 . The EGFR-targeting monoclonal antibody can225IgG (caninized cetuximab) was conjugated to a photosensitizer (IRDye700DX) and tested in canine TCC cell lines, showing specificity and cytotoxic potency.…”