Preclinical biology of recombinant human hemoglobin, rHb1.1.
Historically, the development of hemoglobin based oxygen carriers, HBOCs, were confounded by issues related to activation of the complement cascade and other inflammatory processes, renal toxicity, and significant systemic vasoconstriction. However, with shortages in the blood supply, the risk of infectious agent contamination, and delays associated with complete crossmatch as well as transfusion reactions, HBOC development has assumed greater importance. A successful HBOC in addition to having favorable oxygen binding parameters and colloid oncotic properties, must also have a low toxicity profile, be nonimmunogenic, have positive rheologic properties, and have an adequate in vivo half life. In addition, it must also be stable in vivo and not undergo significant oxidation to methemoglobin or release heme or iron in the vasculature. The preclinical studies which have been designed and executed to address these requirements for recombinant human hemoglobin rHb1.1 serve as the focus of this review. Recombinant Hb1.1 represents the first HBOC to enter clinical trials as a recombinant product in distinction to other HBOCs which are derived from bovine or outdated human blood. While currently in phase II clinical trials, the preclinical biology which has increased our understanding of this molecule are the subject of this review.
Zuckerman
S H
SH
Division of Cardiovascular Research, Lilly Research Labs, Indianapolis, IN, USA.
Doyle
M P
MP
Gorczynski
R
R
Rosenthal
G J
GJ
D000818:Animals; D001802:Blood Substitutes / Q000737:chemistry / Q000633:toxicity; D017322:Clinical Trials, Phase II as Topic; D006455:Hemoglobins, Abnormal / Q000737:chemistry* / Q000235:genetics* / Q000633:toxicity; D006801:Humans; D011994:Recombinant Proteins / Q000737:chemistry* / Q000633:toxicity*
D001802:Blood Substitutes; D006455:Hemoglobins, Abnormal; D011994:Recombinant Proteins; C105876:hemoglobin rHb1.1