Antibody-Conjugated Toxins

 Soon after the discovery of the high specificity of antibody binding, Paul Ehrlich proposed to exploit such specificity to redirect and restrict the activity of toxins to pathological tissues such as tumors (1-3). Such “magic bullets” could be developed only long after his proposal because of the need of antibodies of well-defined specificity, such as monoclonal antibodies, and to improve the understanding of the biochemistry and mechanism of the action of toxins. Such conjugates have been prepared by linking one of the many available cell-killing plant or bacterial toxins via a disulfide or thioether bond to an antibody specific for a cell surface antigen of cancer and noncancer cells. Chimeric toxins have also been prepared by fusing a toxin gene to a gene encoding a hormone, growth factor, or cytokine with the intention of depleting receptor-rich cell populations (1-3). In general, it is important that the linkage between the two immunotoxin parts be easily cleaved on or inside cells. Moreover, to restrict immunotoxin binding only to the cells to be intoxicated, the portion of the toxin determining its intrinsic specificity (the B subunit) must be either deleted or inactivated mutationally, and the F_c portion of the antibody must be removed. In this respect, ribosome-inactivating plant toxins lacking the B subunit have been frequently used. To avoid unspecific binding to F_c-receptor bearing cells, the toxin can be linked to the F(ab)2 portion of a monoclonal antibody. An additional problem may be presented by the presence of circulating antitoxin antibodies elicited in previous vaccination protocols (eg, antidiphtheria) or during the treatment with the immunotoxin. In the latter case, one can use another immunotoxin made with the same antibody and an immunologically unrelated toxin.

 Several antibody-conjugated toxins are very effective in killing target cells in culture or in isolated dispersed tissues, ie, bone marrow, but are less effective in vivo, because of the lack of accessibility of the cancer cells in solid tumors. However, protocols are being developed to overcome these problems and exploit the potentials of immunotoxins to reach small cancer populations that are undetected by physical and surgical methods (3) .

References

1. S. Olsnes, K. Sandvig, O. W. Petersen, and B. van Deurs (1989) Immunol. Today 10, 291–295.

2. D. A. Vallera (1994) Blood 83, 309–317. 

3. G. R. Trush, L. R. Lark, and E. S. Vitetta (1996) Ann. Rev. Immunol. 14, 49–71. 

اخر الاخبار

اخبار العتبة العباسية المقدسة

المجمَع العلمي يطلق الدورة التطويرية الخامسة لمعلمي التربية الإسلامية ومدرسيها في النجف الأشرف

خدمات إنسانية متنوّعة تقدّمها شعبة الشهداء والجرحى في مختلف المحافظات

قسم العلاقات العامة يطلق فعاليات مخيم البذرة الواعدة الخاص بأبناء المنتسبين

جامعة العميد تنظم سلسلة دورات تطويرية لملاكاتها الإدارية

المزيد

الآخبار الصحية

اختراق علمي.. دواء يؤخر ظهور السكري من النوع الأول لسنوات

هذا ما يحدث لجسمك إن أهملت نظافة فراشك

لماذا تعتبر النساء أكثر عرضة للإصابة بألزهايمر من الرجال؟

لماذا يحذر الخبراء من الإفراط في تناول الفراولة؟

المزيد

الآخبار التكنلوجية

السيارات الكهربائية أنظف بنسبة 73% من سيارات الوقود

سيارة لوسِد الكهربائية تدخل "غينيس" بأطول مدى في العالم

نظرية جديدة تنسف كل ما نعرفه عن تشكل أول قارة في الأرض

منذ 37 ألف عام.. دراسة تكشف "أقدم أمراض" أصابت البشر

المزيد

مواضيع ذات صلة

The Yeast Cell Cycle

Structure and Function of TFIIIA

Switching from Oocyte to Somatic 5S Synthesis

Genome Editing of Immune Effector Cells for Safer and More Potent Cancer Therapies (CAR-T Cells)

Therapeutic Genome Editing for Hematologic Diseases: β-Thalassemia

Therapeutic Genome Editing for Hematologic Diseases: Sickle Cell Disease

TFIIIA Binding to the Middle of its Gene as Well as to RNA

Biology of 5S RNA Synthesis in Xenopus

Entropy, a Basis for Lambda Repressor Inactivation

Induction from the Lysogenic State

The Need for and the Realization of Hair-Trigger Induction

Site for Cro Repression and CI Activation