Photosensitizer-antibody conjugates for detection and therapy of cancer.
نویسندگان
چکیده
Photodynamic therapy (PDT) is a promising approach for the treatment of superficially localized tumors. A limitation, however, is the lack of selectivity of the photosensitizers, which can result in severe toxicity. In this overview, the possibilities for using monoclonal antibodies (MAbs) for selective delivery of photosensitizers to tumors, are discussed. This approach is called photoimmunotherapy (PIT). For PIT to be successful, sufficient amounts of sensitizer should be coupled to the MAb without altering its biological properties. A challenging aspect herein is the hydrophobicity of therapeutic photosensitizers. Options for direct and indirect coupling of photosensitizers to MAbs are evaluated, while pros and cons are indicated. Special attention is paid to the quality testing of photoimmunoconjugates, as this information is important for further optimization of PIT. Results obtained thus far with PIT in in vitro and in vivo model systems are discussed. Despite the encouraging progress made, showing the high selectivity of photoimmunoconjugates, PIT still awaits initial clinical evaluation.
منابع مشابه
Gadolinium-Diethylenetriaminepenta-Acetic acid Conjugated with Monoclonal Antibody C595 as New Magnetic Resonance Imaging Contrast Agents for Breast Cancer (MCF-7) Detection
Background: The monoclonal antibody, C595, against breast cancer cell line was conjugated with cyclic anhydride gadolinium-diethylenetriaminepenta-acetic acid (Gd-cDTPAa) to produce Gd-DTPA-C595 and used as specific breast cancer cell line (MCF-7) contrast agents in magnetic resonance imaging (MRI). Methods: After incubation of breast cancer cell line (MCF-7), with different contrast agents (G...
متن کاملProtein-based nanotechnology: antibody conjugated with photosensitizer in targeted anticancer photoimmunotherapy.
Photodynamic therapy (PDT) is a minimally invasive cancer therapy that depends on the buildup of a photosensitizing drug within targeted tissue. The photosensitizer is subsequently activated by light of a specific wavelength, resulting in destruction of the targeted tissue by free radicals or singlet oxygen. Successful treatment requires delivery of critical amounts of drug into the cancerous t...
متن کاملTargeting cancer cells by using an antireceptor antibody-photosensitizer fusion protein.
Antibody-photosensitizer chemical conjugates are used successfully to kill cancer cells in photodynamic therapy. However, chemical conjugation of photosensitizers presents several limitations, such as poor reproducibility, aggregation, and free photosensitizer impurities. Here, we report a fully genetically encoded immunophotosensitizer, consisting of a specific anti-p185(HER-2-ECD) antibody fr...
متن کاملPhotoimmunotherapy of human ovarian carcinoma cells ex vivo.
Photodynamic therapy is a relatively new and potentially selective experimental approach to the treatment of malignant neoplasms. Its inherent dual selectivity is reinforced by the use of photosensitizer-monoclonal antibody conjugates. The goal of this study was to evaluate the phototoxicity and selectivity of an immunoconjugate (IC) synthesized from a chlorin derivative chlorin e6-monoethylene...
متن کاملMALDI-MS: a Rapid and Reliable Method for Drug-to-Antibody Ratio Determination of Antibody-Drug Conjugates
Background: It is believed that the loading value of anticancer drug conjugated to the monoclonal antibody, called drug-to-antibody ratio (DAR), is the main quality feature of antibody-drug conjugates. Methods: In this study, matrix assisted laser desorption/ionization mass spectrometry was used to determine the average molecular weight of trastuzumab and its three conjugated forms. The differe...
متن کاملEvaluation of Factors Influencing Antibody Reduction for Development of Antibody Drug Conjugates
Background: Reduction/alkylation is one of the leading strategies for the development of antibody drug conjugates (ADCs). Precise control of the reduction process would not only yield a defined number of free thiols per antibody but also result in development of more homogenous conjugates. Methods: In the present study, we investigated the effect of various dithiothreitol (DTT) concentrations, ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Advanced drug delivery reviews
دوره 56 1 شماره
صفحات -
تاریخ انتشار 2004