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

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/cm 2 , 8 J/cm 2 , or 16 J/cm 2. 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.

Nanobody: A Small Antibody with Big Implications for Tumor Therapeutic Strategy

“… 146 If the Nb is linked to anti-CEA Nb, it can dissolve CEA + tumor cells through NK cells in vitro models of human cells and tissues, and also suppress cancer cell growth in CEA + tumor transplanted mice, which fosters new thinking on the development of anti-tumor Nb. 147 …”

“…146 If the Nb is linked to anti-CEA Nb, it can dissolve CEA + tumor cells through NK cells in vitro models of human cells and tissues, and also suppress cancer cell growth in CEA + tumor transplanted mice, which fosters new thinking on the development of anti-tumor Nb. 147 There was too much of a correlation between immune infiltration and tumor microenvironment (TME), which has turned out to be enormously successful in clinical cancer immunotherapeutic. 148,149 CAR-T cell therapy is one of the research hotspots of tumor immunotherapy and has a good prospect for the treatment of hematological tumors, which makes patients' own T cells genetically modified to better attack cancer cells (Figure 6B).…”

The Use of Fluorescent Anti-CEA Antibodies to Label, Resect and Treat Cancers: A Review

“…Elekonawo et al used a CEA-expressing human CRC cell line, LoVo, subcutaneously implanted in 18 mice demonstrating labetuzumab-IR700 plus PIT significantly slowed tumor growth compared to PIT alone or labetuzumab-IR700 alone [34]. Hollandsworth et al demonstrated similar findings in an LS174T orthotopic murine model [35].…”

Recent advances in the development of transplanted colorectal cancer mouse models

“…Beyond co-clinical trials, transplant mouse models are also considered useful tools for studying immunotherapy. Hollandsworth et al 97 verified that near-infrared photoimmunotherapy is an effective method for the treatment of CRC using humanized mice. To overcome the limitations of antibody therapy for immune checkpoint blockade, Lee et al 98 explored a novel blockade in traditional oriental medicine, called Sanguisorbae Radix extract (SRE).…”