Variable association of complement activation by rituximab and paclitaxel in cancer patients in vivo and in their screening serum in vitro with clinical manifestations of hypersensitivity: A pilot study

G. Kozma, T. Mészáros, Zsoka Weiszhar, Tamas Schneider, Andras Rosta, Rudolf Urbanics, L. Rosivall, J. Szebeni

Research output: Article

8 Citations (Scopus)

Abstract

To explore the role of complement (C) activation in the hypersensitivity reactions (HSRs) to some anticancer drugs, as well as the use of the C activation biomarkers (Cbiom) C3a, C5a and SC5b-9 in the prediction of HSRs, we measured these Cbiom in plasma samples of cancer patients during infusion therapy, and in their pretreatment (screening) serum incubated with these drugs in vitro. Rituximab and paclitaxel caused mild to severe HSRs in 8/20 and 4/4 patients, respectively, which were associated with rises or falls of plasma and/or serum Cbioms. Among these changes, a rise of C3a in the plasma of 8/8 rituximab reactors and strong rises of Cbioms in the screening sera of all paclitaxel patents were most prominent. However, in the case of rituximab, significant Cbiom changes were also seen in nonreactors, while Cbiom changes were absent in the screening serum. Thus, C activation may be causally involved, but it is not rate limiting factor to HSRs to rituximab. Additional initial data in this study suggest that a whole blood assay using hirudin is more sensitive to C activation by rituximab than the serum test; that trastuzumab and docetaxel also cause HSRs with changes of Cbioms, and that an anti-paclitaxel antibody (ADA) ELISA may be useful as a predictor test for HSRs to Paclitaxel.

Original languageEnglish
Pages (from-to)289-301
Number of pages13
JournalEuropean Journal of Nanomedicine
Volume7
Issue number4
DOIs
Publication statusPublished - nov. 1 2015

Fingerprint

Complement Activation
Paclitaxel
complement
serums
Screening
Hypersensitivity
screening
cancer
Chemical activation
Association reactions
activation
biomarkers
Biomarkers
Serum
Neoplasms
docetaxel
Plasmas
drugs
Hirudins
Patents

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Physical and Theoretical Chemistry
  • Biomedical Engineering

Cite this

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title = "Variable association of complement activation by rituximab and paclitaxel in cancer patients in vivo and in their screening serum in vitro with clinical manifestations of hypersensitivity: A pilot study",
abstract = "To explore the role of complement (C) activation in the hypersensitivity reactions (HSRs) to some anticancer drugs, as well as the use of the C activation biomarkers (Cbiom) C3a, C5a and SC5b-9 in the prediction of HSRs, we measured these Cbiom in plasma samples of cancer patients during infusion therapy, and in their pretreatment (screening) serum incubated with these drugs in vitro. Rituximab and paclitaxel caused mild to severe HSRs in 8/20 and 4/4 patients, respectively, which were associated with rises or falls of plasma and/or serum Cbioms. Among these changes, a rise of C3a in the plasma of 8/8 rituximab reactors and strong rises of Cbioms in the screening sera of all paclitaxel patents were most prominent. However, in the case of rituximab, significant Cbiom changes were also seen in nonreactors, while Cbiom changes were absent in the screening serum. Thus, C activation may be causally involved, but it is not rate limiting factor to HSRs to rituximab. Additional initial data in this study suggest that a whole blood assay using hirudin is more sensitive to C activation by rituximab than the serum test; that trastuzumab and docetaxel also cause HSRs with changes of Cbioms, and that an anti-paclitaxel antibody (ADA) ELISA may be useful as a predictor test for HSRs to Paclitaxel.",
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author = "G. Kozma and T. M{\'e}sz{\'a}ros and Zsoka Weiszhar and Tamas Schneider and Andras Rosta and Rudolf Urbanics and L. Rosivall and J. Szebeni",
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T1 - Variable association of complement activation by rituximab and paclitaxel in cancer patients in vivo and in their screening serum in vitro with clinical manifestations of hypersensitivity

T2 - A pilot study

AU - Kozma, G.

AU - Mészáros, T.

AU - Weiszhar, Zsoka

AU - Schneider, Tamas

AU - Rosta, Andras

AU - Urbanics, Rudolf

AU - Rosivall, L.

AU - Szebeni, J.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - To explore the role of complement (C) activation in the hypersensitivity reactions (HSRs) to some anticancer drugs, as well as the use of the C activation biomarkers (Cbiom) C3a, C5a and SC5b-9 in the prediction of HSRs, we measured these Cbiom in plasma samples of cancer patients during infusion therapy, and in their pretreatment (screening) serum incubated with these drugs in vitro. Rituximab and paclitaxel caused mild to severe HSRs in 8/20 and 4/4 patients, respectively, which were associated with rises or falls of plasma and/or serum Cbioms. Among these changes, a rise of C3a in the plasma of 8/8 rituximab reactors and strong rises of Cbioms in the screening sera of all paclitaxel patents were most prominent. However, in the case of rituximab, significant Cbiom changes were also seen in nonreactors, while Cbiom changes were absent in the screening serum. Thus, C activation may be causally involved, but it is not rate limiting factor to HSRs to rituximab. Additional initial data in this study suggest that a whole blood assay using hirudin is more sensitive to C activation by rituximab than the serum test; that trastuzumab and docetaxel also cause HSRs with changes of Cbioms, and that an anti-paclitaxel antibody (ADA) ELISA may be useful as a predictor test for HSRs to Paclitaxel.

AB - To explore the role of complement (C) activation in the hypersensitivity reactions (HSRs) to some anticancer drugs, as well as the use of the C activation biomarkers (Cbiom) C3a, C5a and SC5b-9 in the prediction of HSRs, we measured these Cbiom in plasma samples of cancer patients during infusion therapy, and in their pretreatment (screening) serum incubated with these drugs in vitro. Rituximab and paclitaxel caused mild to severe HSRs in 8/20 and 4/4 patients, respectively, which were associated with rises or falls of plasma and/or serum Cbioms. Among these changes, a rise of C3a in the plasma of 8/8 rituximab reactors and strong rises of Cbioms in the screening sera of all paclitaxel patents were most prominent. However, in the case of rituximab, significant Cbiom changes were also seen in nonreactors, while Cbiom changes were absent in the screening serum. Thus, C activation may be causally involved, but it is not rate limiting factor to HSRs to rituximab. Additional initial data in this study suggest that a whole blood assay using hirudin is more sensitive to C activation by rituximab than the serum test; that trastuzumab and docetaxel also cause HSRs with changes of Cbioms, and that an anti-paclitaxel antibody (ADA) ELISA may be useful as a predictor test for HSRs to Paclitaxel.

KW - Anaphylaxis

KW - anti-drug antibodies

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KW - immunogenicity

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