Therapeutic Polyclonal Antibodies

The advantage of polyclonal antibodies lies in a higher tolerance towards minor changes of the antigen, as a slightly modified antigen will most probably also be recognized. Polyclonal antibodies as therapeutics are also used if the specific epitope is not established due to practical or financial reasons. 

Polyclonal antibodies however, also have some drawbacks. Due to the non-human molecular heterogeneity, unspecific reactions are likely to occur and may cause a large variety of adverse reactions. In addition, the dose to be administered to target a specific antigen is relatively high compared to that for mAbs this is due to the heterogeneity in specificity and affinity. Furthermore, the immune system will produce anti-antibodies to attack the non-human structures on polyclonal therapeutic antibodies, thereby potentially leading to serious hypersensitivity reactions. 

The antithymocyte globulin (ATG) Fresenius S, produced in rabbits, is an example of a polyclonal antibody mixture used in immunosuppressive therapy in combination with other immunosuppressive agents (e.g., cyclosporine, prednisone) after organ transplantation. 

---

In summary, only a few therapeutic polyclonal antibodies are still marketed today. The main advantages of mAbs are their high specificity towards the target and the capability of an unlimited production of these homogeneous biological molecules. In future, new antibody or antibody-derived pharmaceuticals will be developed and can be expected to have favorable efficacy, a lack of immunogeni-city, and appropriate pharmacokinetics such that they can be used to treat intracellular medical disorders. 

Polyclonal antibody preparations have been used for several decades to induce passive immunization against infectious diseases and other harmful agents, particularly toxins. The antibody preparations are usually administered by direct i.v. injection. While this affords immediate immunological protection, its effect is transitory, usually persisting for only 2-3 weeks (i.e. until the antibodies are excreted). Passive immunization can be used prophylactically (i.e. to prevent a future medical episode) or therapeutically (i.e. to treat a medical condition that is already established). An example of the former would be prior administration of a specific anti-snake toxin antibody preparation to an individual before they travel to a world region in which these snakes are commonly found. An example of the latter would be administration of the anti-venom antibody immediately after the individual has experienced a snake bite. 

The major polyclonal antibody preparations used therapeutically are listed in Table 13.1. These may generally be categorized into one of several groups upon the basis of their target specificities. These groups include antibodies raised against ... 

Although polyclonal antibodies have been used for passive immunization and therapeutic treatments, there are cases when hypersensitivities are induced. The reason is that polyclonal antibodies contain not only the specific antibody that binds to the desired antigen but other antibodies, which our immune system will treat as foreign substances and act against. 

Therapeutic antibodies must be distinguished as mAbs (and derived products) and polyclonal antibodies when discussing their different pharmacokinetic properties and therapeutic applications. mAbs are already - and will in the future - be much more important in drug development and applied pharmacotherapy due to their favorable properties and higher clinical success rates compared to polyclonal antibodies. Thus, although both types of antibody will be discussed in the following sections, most emphasis will be placed on mAbs. 

Compared to polyclonal antibodies, mAbs display molecular homogeneity and significantly higher specificity leading to increased in-vivo activity. For example, 100-170 mg serum containing polyclonal antibodies against the tetanus toxin are necessary to achieve the same effect as 0.7 mg of a respective mAb. This section will provide an overview on therapeutic antibodies which have either been approved or are in clinical development, and will classify them according to different pharmacodynamically relevant properties. 

Traditionally, antibodies for immunoassays have been obtained from the antisera of animals immunized with the Ag of interest. Such antisera contain a collection of different antibodies called polyclonal antibodies, each specific for a different site (epitope) of the Ag. An Ag typically needs to be greater than approximately 1500 Daltons (Da) to elicit efficient Ab formation [1]. However, antibodies for smaller molecules, such as therapeutic drugs, can be obtained by covalently attaching the smaller molecule (hapten) to... 

A quite different approach to immunomodulation is the intravenous use of polyclonal human immunoglobulin. This immunoglobulin preparation (usually IgG) is prepared from pools of thousands of healthy donors, and no specific antigen is the target of the "therapeutic antibody." Rather, one expects that the pool of different antibodies will have a normalizing effect upon the patient s immune networks. 

---