Selective Photokilling of Colorectal Tumors by Near-Infrared Photoimmunotherapy with a GPA33-Targeted Single-Chain Antibody Variable Fragment Conjugate

Wei, Danfeng; Tao, Ze; Shi, Qiuxiao; Wang, Lijun; Liu, Lei; She, Tianshan; Yi, Qiu; Wen, Xiang; Li, Shengfu; Yang, Hao; Jiang, Xian

doi:10.1021/acs.molpharmaceut.0c00210

Cited by 23 publications

(17 citation statements)

References 44 publications

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“…Reducing the circulation time is thus of great importance. Therefore, new PS-conjugate constructs have been synthesized that made use of antibody fragments [ 288 , 289 , 290 ].…”

Section: How To Tame the Bulletmentioning

confidence: 99%

A Photosensitized Singlet Oxygen (1O2) Toolbox for Bio-Organic Applications: Tailoring 1O2 Generation for DNA and Protein Labelling, Targeting and Biosensing

et al. 2022

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Singlet oxygen (1O2) is the excited state of ground, triplet state, molecular oxygen (O2). Photosensitized 1O2 has been extensively studied as one of the reactive oxygen species (ROS), responsible for damage of cellular components (protein, DNA, lipids). On the other hand, its generation has been exploited in organic synthesis, as well as in photodynamic therapy for the treatment of various forms of cancer. The aim of this review is to highlight the versatility of 1O2, discussing the main bioorganic applications reported over the past decades, which rely on its production. After a brief introduction on the photosensitized production of 1O2, we will describe the main aspects involving the biologically relevant damage that can accompany an uncontrolled, aspecific generation of this ROS. We then discuss in more detail a series of biological applications featuring 1O2 generation, including protein and DNA labelling, cross-linking and biosensing. Finally, we will highlight the methodologies available to tailor 1O2 generation, in order to accomplish the proposed bioorganic transformations while avoiding, at the same time, collateral damage related to an untamed production of this reactive species.

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“…Reducing the circulation time is thus of great importance. Therefore, new PS-conjugate constructs have been synthesized that made use of antibody fragments [ 288 , 289 , 290 ].…”

Section: How To Tame the Bulletmentioning

confidence: 99%

A Photosensitized Singlet Oxygen (1O2) Toolbox for Bio-Organic Applications: Tailoring 1O2 Generation for DNA and Protein Labelling, Targeting and Biosensing

et al. 2022

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“…Additionally, GPA33 exhibits limited expression in the normal intestinal epithelium [ 98 ]. GPA33-targeted NIR-PIT demonstrated tumor growth suppression in a xenograft model [ 99 ].…”

Section: Nir-pit Targeting Cancer Cellsmentioning

confidence: 99%

Near Infrared Photoimmunotherapy; A Review of Targets for Cancer Therapy

Kato

Wakiyama

Furusawa

et al. 2021

Cancers

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Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that uses an antibody-photoabsorber (IRDye700DX) conjugate (APC) that is activated by NIR light irradiation. In September 2020, the first APC and laser system were conditionally approved for clinical use in Japan. A major benefit of NIR-PIT is that only APC-bound cancer cells that are exposed to NIR light are killed by NIR-PIT; thus, minimal damage occurs in adjacent normal cells. These early trials have demonstrated that in addition to direct cell killing, there is a significant therapeutic host immune response that greatly contributes to the success of the therapy. Although the first clinical use of NIR-PIT targeted epidermal growth factor receptor (EGFR), many other targets are suitable for NIR-PIT. NIR-PIT has now been applied to many cancers expressing various cell-surface target proteins using monoclonal antibodies designed to bind to them. Moreover, NIR-PIT is not limited to tumor antigens but can also be used to kill specific host cells that create immune-permissive environments in which tumors grow. Moreover, multiple targets can be treated simultaneously with NIR-PIT using a cocktail of APCs. NIR-PIT can be used in combination with other therapies, such as immune checkpoint inhibitors, to enhance the therapeutic effect. Thus, NIR-PIT has great potential to treat a wide variety of cancers by targeting appropriate tumor cells, immune cells, or both, and can be augmented by other immunotherapies.

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“…A fully humanised anti-GPA33 Ab has been reported [ 103 ], conjugated with different radioactive isotopes [ 104 , 105 ] and tested in clinical trials [ 106 ]. The corresponding scFv (scFvA33) has also been combined with different therapeutic agents [ 107 , 108 ] or included in bispecific Ab designs such as the dual-affinity re-targeting antibody (DART) format [ 109 ].…”

Section: Targets In Crcmentioning

confidence: 99%

Antibody-Based Immunotoxins for Colorectal Cancer Therapy

et al. 2021

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Monoclonal antibodies (mAbs) are included among the treatment options for advanced colorectal cancer (CRC). However, while these mAbs effectively target cancer cells, they may have limited clinical activity. A strategy to improve their therapeutic potential is arming them with a toxic payload. Immunotoxins (ITX) combining the cell-killing ability of a toxin with the specificity of a mAb constitute a promising strategy for CRC therapy. However, several important challenges in optimizing ITX remain, including suboptimal pharmacokinetics and especially the immunogenicity of the toxin moiety. Nonetheless, ongoing research is working to solve these limitations and expand CRC patients’ therapeutic armory. In this review, we provide a comprehensive overview of targets and toxins employed in the design of ITX for CRC and highlight a wide selection of ITX tested in CRC patients as well as preclinical candidates.

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Selective Photokilling of Colorectal Tumors by Near-Infrared Photoimmunotherapy with a GPA33-Targeted Single-Chain Antibody Variable Fragment Conjugate

Cited by 23 publications

References 44 publications

A Photosensitized Singlet Oxygen (1O2) Toolbox for Bio-Organic Applications: Tailoring 1O2 Generation for DNA and Protein Labelling, Targeting and Biosensing

A Photosensitized Singlet Oxygen (1O2) Toolbox for Bio-Organic Applications: Tailoring 1O2 Generation for DNA and Protein Labelling, Targeting and Biosensing

Near Infrared Photoimmunotherapy; A Review of Targets for Cancer Therapy

Antibody-Based Immunotoxins for Colorectal Cancer Therapy

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