Protein engineering to target complement evasion in cancer

FEBS Lett. 2014 Jan 21;588(2):334-40. doi: 10.1016/j.febslet.2013.11.007. Epub 2013 Nov 14.

Abstract

The complement system is composed of soluble factors in plasma that enhance or "complement" immune-mediated killing through innate and adaptive mechanisms. Activation of complement causes recruitment of immune cells; opsonization of coated cells; and direct killing of affected cells through a membrane attack complex (MAC). Tumor cells up-regulate complement inhibitory factors - one of several strategies to evade the immune system. In many cases as the tumor progresses, dramatic increases in complement inhibitory factors are found on these cells. This review focuses on the classic complement pathway and the role of major complement inhibitory factors in cancer immune evasion as well as on how current protein engineering efforts are being employed to increase complement fixing or to reverse complement resistance leading to better therapeutic outcomes in oncology. Strategies discussed include engineering of antibodies to enhance complement fixation, antibodies that neutralize complement inhibitory proteins as well as engineered constructs that specifically target inhibition of the complement system.

Keywords: CD46; CD55; CD59; Complement inhibition; Tumor immune evasion.

Publication types

  • Review

MeSH terms

  • Animals
  • Complement System Proteins / immunology*
  • Humans
  • Molecular Targeted Therapy / methods*
  • Neoplasms / drug therapy*
  • Neoplasms / immunology*
  • Protein Engineering / methods*
  • Translational Medical Research
  • Tumor Escape*

Substances

  • Complement System Proteins