Intro: Antibody engineering

Posted: April 15, 2013 in Immunology
Tags: , ,

antibodyengineering

Antibody(AB) is useful tool for research and medicine ( diagnosis & therapy). In fact it emerged in the mid 1990’s as a new drug class .   AB was approved for therapeutic use in clinical setting such as

  • oncology;
  • chronic inflammatory diseases;
  • transplantation;
  • infectious diseases and
  • cardiovascular medicine

One of the biggest advantage of AB use is the high success rate from first use in humans.

  • 29%  chimeric AB
  •  25% humanized AB
  • this is compares favorably with 11% success rate of small molecule drugs

In general AB are well tolerated by humans although infusion reactions( fever, chills e.g patients treated with rituximab CD20 specific monoclonal AB) particularly for first dose are common but manageable. And key strength of AB as therapeutics is their clinical potential can be readily be increased by improving their existing properties.

AB limitations of therapeutics

  1.  restriction of targets to those  on surface or exterior of host cells or invading pathogens
  2. AB drugs are expensive which limits its use to serious medical conditions. Many factors contribute to high cost a) large expense of drug development in general, b) high cost of manufacturing and c) large total doses that are often required.
  3. although AB therapeutics often safe and well tolerated, rare but serious adverse events have been reported.

Goal for AB therapeutics

One need is to improve the efficacy of AB therapeutics e.g anticancer therapy, for which AB are seldom( if ever) curative. Therefore in oncology, one of the goals of increasing efficacy of AB is to improve, antitumour activity and improve patient survival.

  • How? by increasing frequency of partial responses or more preferably , complete responses and by extending the duration of responses.

To improve safety, might be useful to focus on limiting first infusion reactions or more serious target related adverse events

  • e.g  acute and severe influenza- like syndrome associated with adminstration of CD3 specific monoclonal AB= due to Fc-mediated and can be overcome…
  • how? by attenuating the interaction between Fc region of AB and receptors for AB(e.g IgG receptors: FcγRs) expressed by patient

Increasing the potency of AB or extending its half-life in plasma might allow dose or frequency of administration to be reduced, which might have associated benefits  e.g improved quality of life and/or convenience for patient and or reduced cost of drug.

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