Protein engineering to target complement evasion in cancer

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 membra...

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Bibliographic Details
Published in:FEBS letters 2014-01, Vol.588 (2), p.334-340
Main Authors: Carter, Darrick, Lieber, André
Format: Article
Language:English
Subjects:
Animals
CD46
CD55
CD59
Complement inhibition
Complement System Proteins - immunology
Humans
Molecular Targeted Therapy - methods
Neoplasms - drug therapy
Neoplasms - immunology
Protein Engineering - methods
Translational Medical Research
Tumor Escape
Tumor immune evasion
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Summary: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.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2013.11.007