Transplantation method to increase the establishment rate of human tumors in immunodeficient mice
Inventors
Hoffman, Robert M. • Hozumi, Chihiro
Assignees
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Publication Number
US-11871731-B2
Publication Date
2024-01-16
Expiration Date
Abstract
A transplantation method to increase the establishment rate of human tumors in immunodeficient mice. A pocket is created in the mouse and the tumor and surrounding tissues are implanted in the pocket. The pocket is left open to oxygenate the tumor and surrounding tissues.
Core Innovation
The invention provides an improved method of transplanting a tumor of a patient in an immunodeficient mouse. The method includes making at least one incision in the immunodeficient mouse to form at least one pocket, and inserting at least one fragment comprising the tumor and surrounding normal tissues of the tumor into the at least one pocket. The surrounding normal tissues comprise at least all normal tissues in contact with the tumor before preparing the fragment, and these normal tissues are not removed and remain intact.
The surrounding normal tissues together with the transplanted tumor form a macro- and micro-environment of the transplanted tumor. The incision is left open so that the tumor and surrounding tissues are oxygenated, and the surrounding normal tissue and tumor co-implanted together are in contact with each other. This approach aims to establish patient-like tumor tissue conditions in the immunodeficient mouse.
The disclosed embodiment includes use of human patient tumors implanted into immunodeficient mice including nude mice. The described tumor implantation method uses tumor fragments together with surrounding tissues that are not removed so the implanted tissue retains patient-like macro- and micro-environment, and it reports Example 1 establishing 18/20 tumors with a 90% establishment rate after implantation without pretreatment. The disclosure further indicates optional use of more than one pocket/incision and multiple fragments.
Claims Coverage
The independent claim (clm-00001) broadly covers a method for transplanting a patient tumor into an immunodeficient mouse by co-implanting an intact tumor fragment together with surrounding normal tissues that preserve a macro- and micro-environment, while leaving the incision open to allow oxygenation. The claim is supported by multiple dependent refinements that add specific mouse types, surrounding tissue categories, selected tumor types, and quantitative geometric constraints.
Incision-formed pocket receiving tumor fragment with surrounding normal tissues
Making at least one incision in the immunodeficient mouse to form at least one pocket, and inserting at least one fragment comprising the tumor and surrounding normal tissues into the at least one pocket.
Surrounding normal tissues retained intact to form macro- and micro-environment
The surrounding normal tissues comprise at least all normal tissues in contact with the tumor before preparing the at least one fragment, the normal tissues surrounding the tumor are not removed and remain intact, and the surrounding normal tissues form a macro- and micro-environment of the transplanted tumor.
Open incision for oxygenation with co-implanted tissue contact
Leaving the at least one incision open thereby allowing the tumor and surrounding tissues to be oxygenated, wherein the surrounding normal tissue and tumor co-implanted together are in contact with each other.
Nude immunodeficient mouse
Carrying out the method with an immunodeficient mouse that is a nude mouse.
Surrounding tissues including fat and/or necrotic tissue
The surrounding tissues comprise fat tissue and/or necrotic tissue.
Selected tumor types
Selecting the tumor type from breast cancer, ovarian cancer, uterine cancer, cervical cancer, and lung cancer.
Incision length constraint
Wherein the at least one incision has an incision length between 1 mm and 15 mm.
Fragment length constraint
Wherein a fragment has a fragment length of 10 mm.
Overall, the claim set centers on co-implantation of a tumor fragment with surrounding normal tissues that are not removed and remain intact to preserve a macro- and micro-environment, while leaving an incision open to permit oxygenation, with dependent features refining the mouse subtype, tissue categories, tumor types, and dimensional constraints.
Stated Advantages
Allows the implanted tumor and surrounding tissues to be oxygenated by leaving the incision open.
Maintains a macro- and micro-environment of the transplanted tumor by retaining surrounding normal tissues that remain intact and form the macro- and micro-environment.
Documented Applications
Establishing human patient tumors in immunodeficient mice (including nude mice) by implanting tumor fragments with surrounding tissues that are not removed so the implanted tissue retains patient-like macro- and micro-environment.
Example 1 reporting tumor establishment of 18/20 tumors (90% establishment rate) after implantation without pretreatment.
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