Photosensitizer Antibody–Drug Conjugates: Past, Present, and Future

Sandland, Jordon; Boyle, Ross W.

doi:10.1021/acs.bioconjchem.9b00055

Cited by 66 publications

(59 citation statements)

References 199 publications

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“…Several major routes of bioconjugation using linkage pathways have been described, with the most relevant to PDT being cysteine coupling, lysine coupling, and "click" chemistry [24]. These have been described at length in other reviews [170,171], and so will be covered briefly here.…”

Section: Chemical Linkage Methodsmentioning

confidence: 99%

“…A lysine coupling route utilized in bioconjugation is amide conjugation. Perhaps the most utilized method is the use of photosensitizers activated with NHS esters to bind amines on lysine residues of targeting peptides and antibodies [24]. Click chemistry is most often via the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction.…”

Section: Chemical Linkage Methodsmentioning

confidence: 99%

“…Examples of these include chlorins, benzoporphyrins, and phthalocyanines. Most relevant to this review is the third generation of photosensitizers, which are bioconjugated organic (chemical) photosensitizers with a targeting peptide or antibody ( Figure 1; Table 1), thus allowing for increased specificity of phototoxic effects on targeted pathological tissue [24]. More importantly, we want to emphasize the importance of fluorescent protein photosensitizers [25][26][27][28][29][30][31] as a new category of photosensitizer, and their potential use in making novel, targeted fluorescent fusion protein photosensitizers for both PDD and PDT of cancer ( Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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Current Targets and Bioconjugation Strategies in Photodynamic Diagnosis and Therapy of Cancer

Gómez

Tsung

2020

Molecules

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Photodynamic diagnosis (PDD) and therapy (PDT) are emerging, non/minimally invasive techniques for cancer diagnosis and treatment. Both techniques require a photosensitizer and light to visualize or destroy cancer cells. However, a limitation of conventional, non-targeted PDT is poor selectivity, causing side effects. The bioconjugation of a photosensitizer to a tumor-targeting molecule, such as an antibody or a ligand peptide, is a way to improve selectivity. The bioconjugation strategy can generate a tumor-targeting photosensitizer conjugate specific for cancer cells, or ideally, for multiple tumor compartments to improve selectivity and efficacy, such as cancer stem cells and tumor neovasculature within the tumor microenvironment. If successful, such targeted photosensitizer conjugates can also be used for specific visualization and detection of cancer cells and/or tumor angiogenesis (an early event in tumorigenesis) with the hope of an early diagnosis of cancer. The purpose of this review is to summarize some current promising target molecules, e.g., tissue factor (also known as CD142), and the currently used bioconjugation strategies in PDT and PDD, with a focus on newly developed protein photosensitizers. These are genetically engineered photosensitizers, with the possibility of generating a fusion protein photosensitizer by recombinant DNA technology for both PDT and PDD without the need of chemical conjugation. We believe that providing an overview of promising targets and bioconjugation strategies will aid in driving research in this field forward towards more effective, less toxic, and non- or minimally invasive treatment and diagnosis options for cancer patients.

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Section: Chemical Linkage Methodsmentioning

confidence: 99%

Section: Chemical Linkage Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Current Targets and Bioconjugation Strategies in Photodynamic Diagnosis and Therapy of Cancer

Gómez

Tsung

2020

Molecules

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“…Besides increased selectivity, other potential advantages of PIT over conventional therapy with MAB alone or with MAB coupled to radioisotopes, drugs, or toxins are (i) since it is primarily used as a carrier, the MABs do not require any in vivo effector activity (e.g., complement fixation); (ii) in contrast to most drugs and toxins, the PS can act at the cell membrane as well as intracellularly [96]; (iii) PIT may stimulate the host immune response which may help eliminate the tumor as demonstrated by Steele et al [97] using MAB-HP conjugates. Since the initial report by Mew et al [98], we [14,20,86,[99][100][101][102] and others [57,[103][104][105][106][107][108] have demonstrated the feasibility of PICs for the preferential killing of selected cell populations in various systems [16,19,86,[109][110][111]. In the 1990s, Schmidt et al [23,24] prepared PICs of MABs recognizing CA125 on human OvCa cells and performed pilot studies of PIT in OvCa patients.…”

Section: Pic Design Considerationsmentioning

confidence: 99%

Photoimmunotherapy of Ovarian Cancer: A Unique Niche in the Management of Advanced Disease

Nath

Ahsan

Pigula

et al. 2019

Cancers

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Ovarian cancer (OvCa) is the leading cause of gynecological cancer-related deaths in the United States, with five-year survival rates of 15–20% for stage III cancers and 5% for stage IV cancers. The standard of care for advanced OvCa involves surgical debulking of disseminated disease in the peritoneum followed by chemotherapy. Despite advances in treatment efficacy, the prognosis for advanced stage OvCa patients remains poor and the emergence of chemoresistant disease localized to the peritoneum is the primary cause of death. Therefore, a complementary modality that is agnostic to typical chemo- and radio-resistance mechanisms is urgently needed. Photodynamic therapy (PDT), a photochemistry-based process, is an ideal complement to standard treatments for residual disease. The confinement of the disease in the peritoneal cavity makes it amenable for regionally localized treatment with PDT. PDT involves photochemical generation of cytotoxic reactive molecular species (RMS) by non-toxic photosensitizers (PSs) following exposure to non-harmful visible light, leading to localized cell death. However, due to the complex topology of sensitive organs in the peritoneum, diffuse intra-abdominal PDT induces dose-limiting toxicities due to non-selective accumulation of PSs in both healthy and diseased tissue. In an effort to achieve selective damage to tumorous nodules, targeted PS formulations have shown promise to make PDT a feasible treatment modality in this setting. This targeted strategy involves chemical conjugation of PSs to antibodies, referred to as photoimmunoconjugates (PICs), to target OvCa specific molecular markers leading to enhanced therapeutic outcomes while reducing off-target toxicity. In light of promising results of pilot clinical studies and recent preclinical advances, this review provides the rationale and methodologies for PIC-based PDT, or photo-immunotherapy (PIT), in the context of OvCa management.

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“…The conventional treatment using only PS and light is called photodynamic therapy (PDT), which can destroy cells nonspecifically when exposed to light (23). Related to this, PIT is the targeted form of conventional PDT, achieved through the conjugation of PS with MAbs targeting specific cell surface receptors (25,26). PIT can also 4 reduce other issues, such as dark toxicity and PS aggregation in aqueous media which reduce PDT efficacy (14).…”

Section: Introductionmentioning

confidence: 99%

Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates Against HIV Env-Expressing Cells

Sadraeian¹,

Bahou²,

Cruz³

et al. 2020

Preprint

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Different therapeutic strategies have been investigated to target and eliminate HIV-1-infected cells by using armed antibodies specific to viral proteins, with varying degrees of success. Herein, we propose a new strategy by combining photodynamic therapy (PDT) with HIV Env-targeted immunotherapy, and refer to it as HIV photoimmunotherapy (PIT). A human anti-gp41 antibody (7B2) was conjugated to two photosensitizers with different charges through different linking strategies; “Click” conjugation by using an azide-bearing porphyrin attached via a disulfide bridge linker with a drug-to-antibody ratio (DAR) of exactly 4, and “Lysine” conjugation by using phthalocyanine IRDye 700DX dye with average DARs of 2.1, 3.0 and 4.4. These photo-immunoconjugates (PICs) were compared via biochemical and immunological characterizations regarding the dosimetry, solubility, and cell targeting. Photo-induced cytotoxicity of the PICs were compared using assays for apoptosis, reactive oxygen species (ROS), photo-cytotoxicity, and confocal microscopy. Targeted phototoxicity seems to be primarily dependent on the binding of PS-antibody to the HIV antigen on the cell membrane, whilst being independent of the PS type. This is the first report of the application of PIT for HIV immunotherapy by killing HIV Env-expressing cells.

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Photosensitizer Antibody–Drug Conjugates: Past, Present, and Future

Cited by 66 publications

References 199 publications

Current Targets and Bioconjugation Strategies in Photodynamic Diagnosis and Therapy of Cancer

Current Targets and Bioconjugation Strategies in Photodynamic Diagnosis and Therapy of Cancer

Photoimmunotherapy of Ovarian Cancer: A Unique Niche in the Management of Advanced Disease

Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates Against HIV Env-Expressing Cells

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