Removal of tumor cells from intraoperative autologous blood salvage
Inventors
Lindhofer, Horst • Stroehlein, Michael • Heiss, Markus
Assignees
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Publication Number
US-9605242-B2
Publication Date
2017-03-28
Expiration Date
Abstract
The invention relates to a method performed ex vivo for removal of tumor cells from intraoperatively collected blood salvage, to antibodies and scaffold proteins which mimic antibodies for use in said ex vivo method, to the use of said ex vivo method for removal of tumor cells from intraoperatively collected blood salvage followed by reintroducing the so obtained purified blood salvage or of concentrates of erythrocytes purified by said method to a patient from whom said intra-operatively collected blood was obtained, as well as to blood salvage or a concentrate of erythrocytes, both obtainable by said method for reinfusion to said patient.
Core Innovation
The invention relates to an ex vivo method for removal of tumor cells from blood of a tumor patient, in which intra-operatively salvaged blood is contacted with a crosslinking agent. The crosslinking agent forms a three-dimensional network that comprises tumor cells by specifically binding tumor-cell epitopes, and comprises at least one antibody and/or at least one scaffold protein with multispecific or multivalent binding properties similar to antibodies.
The contacting is for a time period sufficient to form associates by cross-linking tumor cells present in the intra-operatively salvaged blood with the antibody, scaffold protein, or combination thereof. The associates have a size sufficient to be retained by filtration or to be separated by centrifugation, and optionally further comprise cross-linked immune cells and/or other tumor cells.
After associate formation, the method mechanically removes the associates from the intra-operatively salvaged blood and then readministeres the intra-operatively salvaged blood to the patient after mechanical removal. The described approach encompasses removal using filtration or centrifugation based on associate size and is exemplified with EpCAM and catumaxomab/catumaxomab-related targeting in a process that removes tumor cells from erythrocyte concentrates with no detectable residual catumaxomab and reduced cytokine levels.
Claims Coverage
One independent claim is provided in the partial content. It covers a complete workflow of contacting intra-operatively salvaged blood with a crosslinking agent to form size-separable associates, mechanically removing the associates, and readministering the blood to the same patient.
Crosslinking tumor cells into size-separable associates from intra-operatively salvaged blood
Intra-operatively salvaged blood suspected of containing tumor cells is contacted with a crosslinking agent that forms a three-dimensional network comprising the tumor cells. The crosslinking agent comprises an antibody and/or a scaffold protein with multispecific or multivalent binding properties, specifically binds at least one epitope of the tumor cells, and forms associates having a size sufficient to be retained by filtration or separated by centrifugation.
Mechanical removal of associates and readministration of treated salvaged blood
The method mechanically removes the associates from the intra-operatively salvaged blood and readministeres the intra-operatively salvaged blood to the patient after mechanically removing the associates.
The inventive concept is crosslinking tumor cells in intra-operatively salvaged blood into associates suitable for filtration or centrifugation, followed by mechanical removal and readministration. The claim coverage also refers to targeting refinements, associate removal options, and leukocyte adsorption filtering.
Stated Advantages
Reduced processing time versus destructive or depletion approaches.
Removes tumor cells from erythrocyte concentrates in the example process.
No detectable residual catumaxomab in the example process.
Reduced cytokine levels in the example process.
Documented Applications
Intraoperative autologous blood salvage (IBS) with ex vivo tumor-cell removal, including removal of tumor cells from erythrocyte concentrates and readministration of purified blood to the same patient.
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