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From Blood Substitutes, Baxter Healthcare Corp, Round Lake, IL; and
the Department of Immunology, Imperial College School of Medicine, The
Hammersmith Hospital, London, UK.
Diaspirin cross-linked hemoglobin (DCLHb) is an intramolecularly
cross-linked hemoglobin-based oxygen carrier being developed as a
therapy for acute blood loss. We report here the absence of
immunogenicity of DCLHb in patients enrolled in phase II and III
clinical trials of DCLHb. Two very sensitive immunoassays, an
enzyme-linked immunosorbent assay (ELISA) and a Western blot assay,
were developed and validated for this assessment. The DCLHb-antibodies used in these assays were raised in monkeys, had similar affinities for
DCLHb and native human hemoglobin (SFHb), and showed cross-reactivity for subunits of DCLHb and SFHb on the Western blot, suggesting that
these antibodies were elicited as a xenogenic response to the protein.
In the ELISA, the optical density of a patient sample exposed to
DCLHb-coated wells was compared with that of the patient sample exposed
to carbonate buffer-coated wells; an optical density ratio of 1.4 was
established for discriminating between a positive (reactive) or
negative DCLHb antibody response. To date, all of the more than 300 patient specimens (preinfusion and postinfusion) from clinical trials
have exhibited a ratio of less than 1.4, confirming the lack of
preexisting antibodies to DCLHb and clearly showing the absence of
DCLHb antibodies after exposure to this new biologic entity. There has
been no requirement for use of the confirmatory Western blot assay.
Taken together, the results from this study indicate DCLHb is not
immunogenic in humans at doses evaluated clinically.
Blood, Vol. 91 No. 2 (January 15), 1998:
pp. 710-716
This article has been cited by other articles:
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| Copyright © 1998 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
