Modified cells produced by bedside cell modification system and methods for using such cells

Abstract

Modified cells for use in the treatment of a disease, ailment, or medical condition of a patient are produced using a bedside cell modification system. The system includes an apheresis system, a cell modification subsystem, and a reinfusion system. The apheresis system is configured to collect from the patient a blood component comprising target cells. The cell modification subsystem is configured to receive the target cells from the apheresis system and to modify the target cells. The reinfusion system is configured to receive the modified target cells from the cell modification subsystem and to return the modified cells to the patient so as to treat the disease, ailment, or medical condition of the patient.

Description

[0001]MODIFIED CELLS PRODUCED BY BEDSIDE CELL MODIFICATION SYSTEM AND METHODS FOR USING SUCH CELLS DESCRIPTION TECHNICAL FIELD The present disclosure is generally directed to apparatus, systems, and methods for modifying cells and conveying the modified cells to a recipient. More particularly, the present disclosure is directed to modified cells that are produced by bedside cell modification systems and methods for using such cells to treat various diseases, ailments, or medical conditions. BACKGROUND Currently, a closed system for processing cells collected from blood or blood components of a patient and returning them to a patient is possible by utilizing an apheresis or cell collection system (hereinafter referred to as “apheresis system”) and a cell processing system that are specially designed to work together. The patient remains connected to the specialized system for the entire time of the procedure. Accordingly, the patient typically is in a single location, commonly in an inclined chair or bed, which results in such systems being collectively referred to as a bedside cell processing system. The apheresis system may separate and collect particular cells from blood, often referred to as blood components or target cells. The processing system then processes the target cells, and the processed cells are returned to the patient via the apheresis system. An example of this arrangement may be provided by use of the Amicus Extracorporeal Photopheresis (ECP) System (otherwise known as Amicus Blue), which is being developed and tested by Fenwal, Inc. of Lake Zurich, Illinois, which is an affiliate of Fresenius Kabi AG of Bad Homburg, Germany. The Amicus ECP System includes an Amicus apheresis system and a Phelix Photoactivation Device, together with specialized software that permits the Amicus apheresis system to be used to return the processed cells to the patient. Thus, the Phelix cell processing system can only be used to treat cells and return them to the patient if it is used with the Amicus apheresis system and special “return of the cells” software. SUMMARY There are several aspects of the present subject matter which may be embodied separately or together in the devices, systems, and methods described and / or claimed below. These aspects may be employed alone or in combination with other aspects of the subject matter described herein, and the description of these aspects together is not intended to preclude the use of these aspects separately or the claiming of such aspects separately or in different combinations as set forth in the claims appended hereto or later amended. The following summary is to acquaint the reader generally with various potential aspects of the present subject matter, and is non-limiting and non- exclusive with respect to the various possible aspects or combinations of aspects. Additional aspects and features may be found in the detailed description herein and / or in the accompanying figures. Apparatus, systems and methods are disclosed for collecting target cells from a patient, processing or modifying those cells and returning the processed or modified cells to the patient. However, by including an independent reinfusion system, the systems and methods may be agnostic to the capability of the apheresis system. Thus, by including an independent reinfusion system within the closed system that is connected to a patient, any apheresis system may be employed, as well as any suitable cell processing or modification system or subsystem. An apheresis system will collect the target cells. Apheresis or collection systems typically collect biological fluid such as blood or blood components by using a reusable processing apparatus (“hardware”) and a disposable fluid circuit (“kit”) adapted for mounting or other association with the reusable apparatus. After collection of the cells, the apheresis system will return to the patient any cells remaining in the disposable kit used with the apheresis system. This type of reinfusion of such remaining cells is typical of the reinfusion that may be routinely performed by an apheresis system relative to the collection process. The collected target cells meanwhile are being processed or modified via one or more cell processing or modification unit(s) or subsystems. Examples of such units or subsystems may include the Phelix Photoactivation Device, the Cue cell processing system, the Cue cell selection system or transduction system, a washing system, an incubation system, a cell modification system, or other units suitable for processing or modifying cells for various purposes. The Phelix Photoactivation Device and Cue systems are sold by Fenwal, Inc. of Lake Zurich, Illinois, which is an affiliate of Fresenius Kabi AG of Bad Homburg, Germany. Somewhat similarly to the apheresis systems, cell processing or modification systems or subsystems may process or modify cells by using a reusable processing or modification apparatus (“hardware”) and a disposable fluid circuit (“kit”) adapted for mounting or other association with the reusable apparatus. The time required to process or modify cells depends on the procedure selected and the quantity of cells. As such, the processing or modification of cells may take from a few minutes to many hours, during which the patient remains connected to the system. Connection of the patient to the system includes pre- connection of the patient to the separate reinfusion system. Accordingly, after cell processing or modification, the processed or modified cells will be reinfused into the patient via the infusion system. As with the apheresis and cell processing or modification systems, the infusion system may use a reusable apparatus (“hardware”) and a disposable fluid circuit (“kit”) adapted for mounting or other association with the reusable apparatus. The patient remains connected to the apheresis system and the reinfusion system during the procedure. At least three configurations for patient access by the apheresis system and reinfusion system are contemplated and disclosed herein. For example, in a first configuration, the apheresis system and reinfusion system may share a single patient access via a needle or catheter used with a single patient appendage and which is connected to the apheresis system to both collect biological fluid from the patient and to return to the patient cells remaining in the apheresis system kit, while also being connected to the reinfusion system to reinfuse into the patient processed or modified cells. In a second example configuration, the apheresis system may have patient access via a first needle or catheter used with a first patient appendage and which is connected to the apheresis system to collect biological fluid. In the second example, the apheresis system and reinfusion system also may share patient access via a second needle or catheter used with a second patient appendage and which is connected to the apheresis system to return to the patient cells remaining in the apheresis system kit, while being connected to the reinfusion system to reinfuse into the patient processed or modified cells. In the third examplary configuration, the apheresis system may have patient access via a first needle or catheter used with a first patient appendage and which is connected to the apheresis system to both collect biological fluid from the patient and to return to the patient cells remaining in the apheresis system kit, while the reinfusion system has separate patient access via a second needle or catheter used with a second patient appendage and which is connected to the reinfusion system to reinfuse into the patient processed or modified cells. Thus, patient access for the reinfusion system may be via pre-connection along the reinfusion line from the apheresis system, which also may be connected to or separate from the biological fluid collection line. Alternatively patient access for the reinfusion system may be via a reinfusion line that is separate from an apheresis system biological fluid collection and cell return reinfusion line. Having a separate and independent reinfusion system provides an advantage in that the apheresis system selected need not be capable of receiving modified cells from the cell processing or modification system or subsystem and reinfusing such cells into the patient. Any apheresis system may be employed in the closed system to carry out the process. Also, the reinfusion system and the cell processing or modification units or subsystems of the cell processing or modification systems may be connected in a closed system configuration, along with the apheresis system, via sterile connection devices. The reinfusion system may include a microprocessor, memory, input device, output device, pump, one or more sensors and clamps, depending on the desired configuration. The sensors of the reinfusion system may be of types referred to as a venous pressure sensor, cell counter, hemolysis sensor, optical density sensor, or any other suitable sensor for monitoring the quality and / or quantity of cells, or other parameters of interest when reinfusing a patient with processed or modified cells. Thus, the use of a separate, independent reinfusion system facilitates flexibility and the potential use of different apheresis systems and different cell processing or modification systems or subsystems, while still permitting the convenience of a bedside cell processing or modification system. In one aspect, modified cells are provided for use in the treatment of a disease, ailment, or medical condition of a patient. The modified cells are produced using a bedside cell modification system including an apheresis system, a cell modification subsystem, and a reinfusion system. The apheresis system is configured to collect from the patient a blood component comprising target cells. The cell modification subsystem is configured to receive the target cells from the apheresis system and to modify the target cells. The reinfusion system is configured to receive the modified target cells from the cell modification subsystem and to return the modified cells to the patient so as to treat the disease, ailment, or medical condition of the patient. In another aspect, modified cells are provided for use in the treatment of a disease, ailment, or medical condition of a patient. The modified cells are produced at bedside using a method that includes connecting an apheresis system to the patient via a collection flow path, connecting the apheresis system to a cell modification subsystem via a collected target cells flow path, connecting the cell modification subsystem to a reinfusion system via a modified target cells flow path, and connecting the reinfusion system to the patient via a reinfusion system flow path. The apheresis system is operated to collect from the patient via the collection flow path a blood component comprising target cells. The cell modification subsystem is operated to receive the target cells from the apheresis system via the collected target cells flow path and to modify the target cells. The reinfusion system is operated to receive the modified target cells from the cell modification subsystem via the modified target cells flow path and to return the modified target cells to the patient via the reinfusion system flow path so as to treat the disease, ailment, or medical condition of the patient. These and other aspects of the present subject matter are set forth in the following detailed description of the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a schematic diagram of a first example bedside cell processing or modification system having a reinfusion system; Figure 2 is schematic diagram of an exemplary reinfusion system for use in the bedside cell processing or modification system shown in Figure 1; Figure 3 is a schematic diagram of a second exemplary bedside cell processing or modification system having a reinfusion system, such as is shown in Figure 2; and Figure 4 is a schematic diagram of a third exemplary bedside cell processing or modification system having a reinfusion system, such as is shown in Figure 2. DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS It will be appreciated that a bedside cell processing or modification system configured to include a separate reinfusion system for collection, processing or modification, and return of processed or modified cells to a patient may be applicable for efficient and convenient use with a variety of apheresis systems and cell processing or modification systems or subsystems. Figure 1 illustrates a first example embodiment of a bedside cell processing or modification system 10. The bedside cell processing or modification system 10 includes an apheresis system 12 configured to collect from a patient P a blood component comprising target cells, a cell processing or modification system or subsystem 14 configured to receive the target cells from the apheresis system 12 and to process or modify the target cells, and a reinfusion system 16 configured to receive the processed or modified target cells from the cell processing or modification system or subsystem 14 and to return the processed or modified cells to the patient P. Thus, in use, the bedside cell processing or modification system 10 is a closed system to which the patient remains connected throughout the procedure. The apheresis system 12 may be any suitable type of apheresis or cell collection system. Some examples may be the Amicus, Alyx or Aurora systems sold by Fenwal, Inc. of Lake Zurich, Illinois, which is an affiliate of Fresenius Kabi AG of Bad Homburg, Germany. The apheresis system 12 further includes fluid communication access to the patient P via a collection flow path 18. The collection flow path 18 also includes a connection to the patient P via a needle or catheter 20. In the example embodiment shown, the collection flow path 18 further includes a Y-connector 22, and a first flow path 24 between the patient P and the Y-connector 22 and a second flow path 26 between the Y-connector 22 and the apheresis system 12. As previously noted, the apheresis or cell collection system 12 will collect biological fluid such as blood or blood components by using a reusable processing apparatus (“hardware”) and a disposable fluid circuit (“kit”) adapted for mounting or other association with the reusable apparatus. All connections to the kit of the apheresis system 12, such as the needle 20, are via sterile connectors, such as luer lock tubing connectors or suitable alternatives. The example apheresis system 12 also includes fluid communication access to the patient P via an apheresis system reinfusion flow path 28 to return to the patient P cells that remain in the apheresis system 12 after at least a portion of the target cells are received by the cell processing or modification system or subsystem 14. The apheresis system reinfusion flow path may extend directly to the patient, or as shown in the first example embodiment, it may be connected to the collection line 18. Thus, in the example shown in Figure 1, the apheresis system reinfusion flow path 28 further includes a connection to the Y-connector 22 in the collection flow path 18, wherein the first flow path 24 also is used for reinfusion. Indeed, the apheresis system reinfusion flow path 28 may include further connections, such as a Y-connector 30, and a third flow path 32 between the apheresis system 12 and the Y-connector 30 in the apheresis system reinfusion flow path 28 and a fourth flow path 34 between the Y-connector 30 in the apheresis system reinfusion flow path 28 and the Y-connector 22 in the apheresis system collection flow path 18. The cell processing or modification system or subsystem 14 of the bedside cell processing or modification system 10 includes fluid communication with the apheresis system 12 via a collected target cells flow path 36. The cell processing or modification system or subsystem14 processes or modifies the target cells received from the apheresis system 12 using light treatment (photopheresis), cell separation, concentration and / or washing, cell modification (e.g., genetic modification), or any other desired form of cell processing or modification. The cell processing or modification system or subsystem14 may be any suitable type of cell processing or modification system, or any combination of cell processing or modification system units. Some examples may be the Phelix Photoactivation Device, Cue or Lovo systems sold by Fenwal, Inc. of Lake Zurich, Illinois, which is an affiliate of Fresenius Kabi AG of Bad Homburg, Germany, or other suitable processing or modification systems. The cell processing or modification system or subsystem 14 will process or modify the target cells by using a reusable processing or modification apparatus (“hardware”) and a disposable fluid circuit (“kit”) adapted for mounting or other association with the reusable apparatus. All connections to the kit of the cell processing or modification system or subsystem 14, such as to fluid containers or to the apheresis system 12, are via sterile connectors, such as luer lock tubing connectors or suitable alternatives. The reinfusion system 16 of the bedside cell processing or modification system 10 further includes fluid communication with the cell processing or modification system or subsystem 14 via a processed or modified target cells flow path 38. It will be appreciated that the reinfusion system 16 also includes fluid communication access to the patient P to return to the patient processed or modified target cells via a reinfusion system flow path 40. The reinfusion system 16 will reinfuse cells by using a reusable processing apparatus (“hardware”) and a disposable fluid circuit (“kit”) adapted for mounting or other association with the reusable apparatus. All connections to the kit of the reinfusion system 16, such as to the cell processing or modification system or subsystem 14 or to the apheresis system reinfusion flow path or to a needle for connection to the patient, are via sterile connectors, such as luer lock tubing connectors or suitable alternatives. As noted with respect to the apheresis system reinfusion flow path 28 and shown in the first example embodiment in Figure 1, the reinfusion system flow path 40 may be connected to the apheresis system reinfusion flow path 28, utilizing a single patient access point for collection and reinfusion. Thus, as shown in the first example embodiment, the reinfusion system flow path 40 may include a fifth flow path 42 between the reinfusion system 16 and the Y-connector 30 in the apheresis system reinfusion flow path 28. In this example, it will be appreciated that the reinfusion system flow path 40 includes the fifth flow path 42 between the reinfusion system 16 and the Y-connector 30 in the apheresis system reinfusion flow path 28, the fourth flow path 34 between the Y-connector 30 in the apheresis system reinfusion flow path 28 and the Y-connector 22 in the apheresis system collection flow path 18 and the first flow path 24 between the Y-connector 22 in the apheresis system collection flow path 18 and the patient P. As previously noted, the connection to the patient P may be via a needle or catheter 20. An example reinfusion system 16 is further illustrated in Figure 2 and includes a controller 50 having a microprocessor 52 and memory 54. The reinfusion system 16 also includes a pump 56. The reinfusion system 16 further preferably includes at least one sensor 58 and at least one clamp 60. An operator may operate the controller manually or engage an automated program mode via use of an input device 62 and view settings, performance or other data via an output device 64. The at least one sensor 58 may be configured in various forms to monitor desired parameters, such as a venous pressure sensor, a cell counter, a hemolysis sensor and / or an optical density sensor. It will be appreciated that the bedside cell processing or modification system 10 advantageously may be used in a method of operating a bedside cell processing or modification system 10 for a patient P. The method includes connecting an apheresis system 12 to the patient P via a collection flow path 18, connecting the apheresis system 12 to a cell processing or modification system or subsystem 14 via a collected target cells flow path 36, connecting the cell processing or modification system or subsystem 14 to a reinfusion system 16 via a processed or modified target cells flow path 38, connecting the reinfusion system 16 to the patient P via a reinfusion system flow path 40, operating the apheresis system 16 to collect from the patient P via the collection flow path 18 a blood component comprising target cells, operating the cell processing or modification system or subsystem 14 to receive the target cells from the apheresis system 12 via the collected target cells flow path 36 and to process or modify the target cells, and operating the reinfusion system 16 to receive the processed or modified target cells from the cell processing or modification system or subsystem 14 via the processed or modified target cells flow path 38 and to return the processed or modified target cells to the patient P via the reinfusion system flow path 40. In utilizing the method, as described above, the collection flow path 18 may include a connection to the patient P via a needle or catheter 20. The method may further utilize an apheresis system 12 that includes an apheresis system reinfusion flow path 28 to return to the patient P cells that remain in the apheresis system 12 after at least a portion of the target cells are received by the cell processing or modification system or subsystem 14. The apheresis system reinfusion flow path 28 may include a portion of the apheresis system collection flow path 18. For example, the portion of the apheresis system collection flow path 18 included in the apheresis system reinfusion flow path 28 may include a connection to the patient P via a needle or catheter 20, such as via the Y- connector 22 and first flow path 24. The reinfusion system flow path 40 may include a portion of the apheresis system reinfusion flow path 28 and a portion of the apheresis system collection flow path 18. For example, the portion of the apheresis system reinfusion flow path 28 included in the reinfusion system flow path 40 may include a Y-connector 30 and fourth flow path 34 in the apheresis system reinfusion flow path 28. Furthermore, the portion of the apheresis system collection flow path 18 that may be included in the reinfusion system flow path 40 may include the Y-connector 22, the first flow path 24 and the connection to the patient P via a needle or catheter 20. It will be appreciated that operating the bedside cell processing or modification system 10 includes processing or modifying the target cells received from the apheresis system 12 using light treatment (photopheresis), cell separation, concentration and / or washing, cell modification (including, but not limited to, genetic modification), or other suitable forms of cell processing. As used herein, the terms “cell modification” or “modification” or “modified” refers to a process in which target cells are isolated from other cells and then mixed with a modification solution or agent employing an appropriate vector (e.g., mRNA, CRISPR-Cas9, Transposon / Transposase). Electroporation, mechanoporation, sonoporation, or other flow-through transfection methods are employed to introduce the payload to the target cells. In an exemplary embodiment of cell modification, a patient’s T-cells are altered, with an artificial receptor being added to the cells that attach to cancer cell antigens. These modified T-cells are returned to the patient and can help target and destroy specific cancer cells. Exemplary systems that are capable of modifying target cells are described in PCT Patent Application Serial Nos. PCT / US2024 / 015404 and PCT / US2024 / 015424, each of which is hereby incorporated herein by reference. Operating the reinfusion system 16 includes having a controller 50 operate a pump 56 to deliver the processed or modified target cells to the patient P. As described above, the controller 50 of the reinfusion system 16 may include a microprocessor 52 and memory 54. The reinfusion system 16 also may include at least one sensor 58 and at least one clamp 60. It will be appreciated that the at least one sensor 58 may include a venous pressure sensor, a cell counter, a hemolysis sensor and / or an optical density sensor, or other suitable sensors. Moreover, practicing the method of operating a bedside cell processing or modification system 10 for a patient P may include the operator operating the reinfusion system 16 by entering parameters into the controller 50 via an input device 26, such as for manual or automated operation. Figure 3 illustrates a second example embodiment of a bedside cell processing or modification system 110. Similarly to the first example embodiment in Figure 1, the second example embodiment of a bedside cell processing or modification system 110 includes an apheresis system 12 as previously described and configured to collect from a patient P a blood component comprising target cells, a cell processing or modification system or subsystem 14 as previously described and configured to receive the target cells from the apheresis system 12 and to process or modify the target cells, and a reinfusion system 16 as previously described and configured to receive the processed or modified target cells from the cell processing or modification system or subsystem 14 and to return the processed or modified cells to the patient P. Thus, in use, the second example bedside cell processing or modification system 110 also is a closed system to which the patient remains connected throughout the procedure. In the second example bedside cell modification system 110, the apheresis system 12 further includes fluid communication access to the patient P via a collection flow path 118. The collection flow path 118 also includes a connection to the patient PL(example left arm) via a needle or catheter 20L. In the second exemplary embodiment shown, the collection flow path 118 further includes a first flow path 124 between the patient PLand the apheresis system 12. As previously noted, the apheresis or cell collection system 12 will collect biological fluid such as blood or blood components by using a reusable processing apparatus (“hardware”) and a disposable fluid circuit (“kit”) adapted for mounting or other association with the reusable apparatus. All connections to the kit of the apheresis system 12, such as the needle 20L, are via sterile connectors, such as luer lock tubing connectors or suitable alternatives. In the second exemplary bedside cell processing or modification system 110, the example apheresis system 12 also includes fluid communication access to the patient P via an apheresis system reinfusion flow path 128 to return to the patient PR (example right arm) via a needle or catheter 20R cells that remain in the apheresis system 12 after at least a portion of the target cells are received by the cell processing or modification system or subsystem 14. The apheresis system reinfusion flow path may extend directly to the patient PR, or as shown in the second example embodiment, it also may be connected to the reinfusion system 16. Thus, in the second example shown in Figure 2, the apheresis system reinfusion flow path 128 further includes a Y-connector 130, for the apheresis system reinfusion flow path 128 to also be used for reinfusion from the reinfusion system 16. Indeed, the apheresis system reinfusion flow path 128 may include the Y- connector 130, and a second flow path 132 between the apheresis system 12 and the Y-connector 130 in the apheresis system reinfusion flow path 128 and a third flow path 134 between the Y-connector 130 in the apheresis system reinfusion flow path 128 and the needle or catheter 20R. The cell processing or modification system or subsystem 14 of the bedside cell processing or modification system 10 includes fluid communication with the apheresis system 12 via a collected target cells flow path 36. As previously noted, the cell processing or modification system or subsystem 14 processes or modifies the target cells received from the apheresis system 12 by using a reusable processing or modification apparatus (“hardware”) and a disposable fluid circuit (“kit”) and may be any suitable type of cell processing or modification system, or any combination of cell processing or modification system units, with all connections to the kit of the cell processing or modification system or subsystem 14, such as to fluid containers or to the apheresis system 12, being via sterile connectors. Similar to the first example, the reinfusion system 16 of the second example bedside cell processing or modification system 110 further includes fluid communication with the cell processing or modification system or subsystem 14 via a processed or modified target cells flow path 38. It will be appreciated that the reinfusion system 16 also includes fluid communication access to the patient PRto return to the patient processed or modified target cells via a reinfusion system flow path 140. As previously described, the reinfusion system 16 will reinfuse cells by using a reusable processing apparatus (“hardware”) and a disposable fluid circuit (“kit”). All connections to the kit of the reinfusion system 16, such as to the cell processing or modification system or subsystem 14 or to the apheresis system reinfusion flow path or to a needle for connection to the patient, are via sterile connectors, such as luer lock tubing connectors or suitable alternatives. As noted with respect to the apheresis system reinfusion flow path 28 shown in the first example embodiment in Figure 1, the reinfusion system flow path 40 may be connected to the apheresis system reinfusion flow path 28. However, in the second example embodiment in Figure 3, the reinfusion system flow path 140 is connected to the apheresis system flow path 128, and the two utilize a second, separate patient access point for all reinfusion. Thus, as shown in the second example embodiment in Figure 3, the reinfusion system flow path 140 may include a fourth flow path 142 between the reinfusion system 16 and the Y-connector 130 in the apheresis system reinfusion flow path 128. In this second example, it will be appreciated that the reinfusion system flow path 140 includes the fourth flow path 142 between the reinfusion system 16 and the Y-connector 130 in the apheresis system reinfusion flow path 128, the third flow path 134 between the Y-connector 130 in the apheresis system reinfusion flow path 128 and the patient PR. As previously noted, the connection to the patient PR may be via a needle or catheter 20R. The second example bedside cell processing or modification system 110 may utilize the example reinfusion system 16, as illustrated in Figure 2, as above described. Thus, it will be appreciated that the bedside cell processing or modification system 110 advantageously may be used in a method of operating a bedside cell processing or modification system 110 for a patient P. The method includes connecting an apheresis system 12 to the patient PL via a collection flow path 118, connecting the apheresis system 12 to a cell processing or modification system or subsystem 14 via a collected target cells flow path 36, connecting the cell processing or modification system or subsystem 14 to a reinfusion system 16 via a processed or modified target cells flow path 38, connecting the reinfusion system 16 to the patient PRvia a reinfusion system flow path 140, operating the apheresis system 16 to collect from the patient PL via the collection flow path 118 a blood component comprising target cells, operating the cell processing or modification system or subsystem 14 to receive the target cells from the apheresis system 12 via the collected target cells flow path 36 and to process or modify the target cells, and operating the reinfusion system 16 to receive the processed or modified target cells from the cell processing or modification system or subsystem 14 via the processed or modified target cells flow path 38 and to return the processed or modified target cells to the patient PRvia the reinfusion system flow path 140. In utilizing the method, as described above, the collection flow path 118 may include a connection to a first appendage of the patient PLvia a needle or catheter 20L. The method may further utilize an apheresis system 12 that includes an apheresis system reinfusion flow path 128 to return to a second appendage of the patient PR cells that remain in the apheresis system 12 after at least a portion of the target cells are received by the cell processing or modification system or subsystem 14. It will be appreciated that operating the second example bedside cell processing or modification system 110 includes operating the reinfusion system 16, illustrated in Figure 2, in a manner similar to that described for the first example bedside cell processing or modification system 10. Figure 4 illustrates a third exemplary embodiment of a bedside cell processing or modification system 210. Similarly to the first exemplary embodiment in Figure 1, the third exemplary embodiment of a bedside cell processing or modification system 210 includes an apheresis system 12 as previously described and configured to collect from a patient P a blood component comprising target cells, a cell processing or modification system or subsystem 14 as previously described and configured to receive the target cells from the apheresis system 12 and to process or modify the target cells, and a reinfusion system 16 as previously described and configured to receive the processed or modified target cells from the cell processing or modification system or subsystem 14 and to return the processed or modified cells to the patient P. Thus, in use, the third exemplary bedside cell processing or modification system 210 also is a closed system to which the patient remains connected throughout the procedure. In the third exemplary bedside cell processing or modification system 210, the apheresis system 12 further includes fluid communication access to the patient P via a collection flow path 218. The collection flow path 218 also includes a connection to the patient PL(example left arm) via a needle or catheter 20L. In the third example embodiment shown, the collection flow path 218 further includes a Y-connector 222, and a first flow path 224 between the patient PL and the Y- connector 222 and a second flow path 226 between the Y-connector 222 and the apheresis system 12. As previously noted, the apheresis or cell collection system 12 will collect biological fluid such as blood or blood components by using a reusable processing apparatus (“hardware”) and a disposable fluid circuit (“kit”) adapted for mounting or other association with the reusable apparatus. All connections to the kit of the apheresis system 12, such as the needle 20L, are via sterile connectors, such as luer lock tubing connectors or suitable alternatives. The exemplary apheresis system 12 also includes fluid communication access to the patient PL via an apheresis system reinfusion flow path 228 to return to the patient P cells that remain in the apheresis system 12 after at least a portion of the target cells are received by the cell processing or modification system or subsystem 14. The apheresis system reinfusion flow path may extend directly to the patient, or as shown in the third example embodiment, it may be connected to the collection flow path 218. Thus, in the example shown in Figure 4, the apheresis system reinfusion flow path 228 further includes a connection to the Y- connector 222 in the collection flow path 218, wherein the first flow path 224 also is used for reinfusion from the apheresis system. Indeed, the apheresis system reinfusion flow path 228 may include a third flow path 232 between the apheresis system 12 and the Y-connector 222 in the apheresis system collection flow path 218. The cell processing or modification system or subsystem 14 of the third exemplary bedside cell processing or modification system 210 includes fluid communication with the apheresis system 12 via a collected target cells flow path 36. As previously noted, the cell processing or modification system or subsystem 14 processes or modifies the target cells received from the apheresis system 12 by using a reusable processing or modification apparatus (“hardware”) and a disposable fluid circuit (“kit”) and may be any suitable type of cell processing or modification system, or any combination of cell processing or modification system units, with all connections to the kit of the cell processing or modification system 14, such as to fluid containers or to the apheresis system 12, being via sterile connectors. Similar to the first example, the reinfusion system 16 of the third exemplary bedside cell processing or modification system 210 further includes fluid communication with the cell processing or modification system or subsystem 14 via a processed or modified target cells flow path 38. However, it also will be appreciated that the reinfusion system 16 includes fluid communication access to the patient PR (example right arm) via reinfusion system flow path 240, including a fourth flow path 242 and via a needle or catheter 20R to return to the patient processed or modified target cells. As previously described, the reinfusion system 16 will reinfuse cells by using a reusable processing apparatus (“hardware”) and a disposable fluid circuit (“kit”). All connections to the kit of the reinfusion system 16, such as to the cell processing or modification system or subsystem 14 or to the apheresis system reinfusion flow path or to a needle for connection to the patient, are via sterile connectors, such as luer lock tubing connectors or suitable alternatives. Thus, it will be appreciated that the third example bedside cell processing or modification system 210 advantageously may be used in a method of operating a bedside cell processing or modification system 210 for a patient P. The method includes connecting an apheresis system 12 to the patient PLvia a collection flow path 218, connecting the apheresis system 12 to a cell processing or modification system or subsystem 14 via a collected target cells flow path 36, connecting the cell processing or modification system or subsystem 14 to a reinfusion system 16 via a processed or modified target cells flow path 38, connecting the reinfusion system 16 to the patient PRvia a reinfusion system flow path 240, operating the apheresis system 16 to collect from the patient PL via the collection flow path 218 a blood component comprising target cells, operating the cell processing or modification system or subsystem 14 to receive the target cells from the apheresis system 12 via the collected target cells flow path 36 and to process or modify the target cells, and operating the reinfusion system 16 to receive the processed or modified target cells from the cell processing or modification system or subsystem 14 via the processed or modified target cells flow path 38 and to return the processed or modified target cells to the patient PRvia the reinfusion system flow path 240. In utilizing the method, as described above, the collection flow path 218 may include a connection to a first appendage of the patient PL via a needle or catheter 20L. The method may further utilize an apheresis system 12 that includes an apheresis system reinfusion flow path 228 to return to the first appendage of the patient PLcells that remain in the apheresis system 12 after at least a portion of the target cells are received by the cell processing or modification system or subsystem 14. It will be appreciated that operating the third example bedside cell processing or modification system 210 includes operating the reinfusion system 16, illustrated in Figure 2, to then return to the patient processed or modified cells via the reinfusion system flow path 240. Thus, an improved bedside cell processing or modification system and methods of operating the system are disclosed herein. It will be appreciated that the reinfusion system of the disclosed bedside cell processing or modification system may be a separate, independent system, which can be used with any alternative apheresis systems and any alternative cell processing or modification systems or subsystems. The description provided above, and the other aspects provided below, are intended for illustrative purposes, and are not intended to limit the scope of the disclosure to any particular apparatus, system or method described herein. Examples In one embodiment, the modified cells produced by the cell processing or modification system or subsystem include Chimeric Antigen Receptor T-Cells (CAR-T) cells. These CAR-T cells may be used in several applications and therapeutic treatments of various diseases, ailments, or conditions. For example, the CAR-T cells may be used to treat solid tumors such as anal / rectal, epithelial, ovarian, breast, fallopian tube, endometrial, pancreatic, colorectal, lung, and / or gastrointestinal tumors. The CAR-T cells may also be useful in therapeutically treating melanoma, multiple myeloma, acute lymphoblastic leukemia, acute myelocytic lymphoma, non-Hodgkin lymphoma, diffuse large b-cell lymphoma, small-cell lung cancer, neuroblastoma, glioblastoma, prostate cancer, hemophilia, sickle cell disease, lupus erythematosus, lupus nephritis, myasthenia gravis, autoimmune diseases, soft tissue sarcoma, osteosarcoma, hepatocellular carcinoma, graft versus host disease, and rheumatoid arthritis. The CAR-T cells may also be useful for renal transplantation patients. Accordingly, the disclosure provides a modified CAR-T cell produced by the cell processing or modification system or subsystem for use in the treatment of a disease, ailment, or condition selected from the group consisting of solid tumors such as anal / rectal, epithelial, ovarian, breast, fallopian tube, endometrial, pancreatic, colorectal, lung, and / or gastrointestinal tumors; melanoma, multiple myeloma, acute lymphoblastic leukemia, acute myelocytic lymphoma, non-Hodgkin lymphoma, diffuse large b- cell lymphoma, small-cell lung cancer, neuroblastoma, glioblastoma, prostate cancer, hemophilia, sickle cell disease, lupus erythematosus, lupus nephritis, myasthenia gravis, autoimmune diseases, soft tissue sarcoma, osteosarcoma, hepatocellular carcinoma, graft versus host disease, rheumatoid arthritis, and impairments related to renal transplantation. In producing the CAR-T cells, different modification strategies may be used in the cell processing or modification system or subsystem, with the various methods being practiced in the preparation of CAR-T cells for any one of the preceding applications or therapeutic treatments. Vectors such as mRNA, shRNA, siRNA, saRNA, SeekRNA, polymers, proteins and peptides, antibodies, viruses, including but not limited to lentivirus (LV), Adeno Associated Virus (AAV), labelling molecules, small molecules, Virus-like particles (VLP), transposon / transposase (sleeping beauty, TcBuster, PiggyBac), transcription activator-like effector nuclease (TALEN), zinc finger nucleases (ZFN), base editors, prime editors, programmable addition via site-specific targeting elements (PASTE), CRISPR / Cas, and CRISPR RNPs may be utilized in the cell processing or modification system or subsystem to create the CAR-T cells. Accordingly, the disclosure provides in certain embodiments modified CAR-T cells produced by use of the aforementioned vectors for use in the treatment of a disease, ailment, or condition as shown in Tables 1 and 2: Table 1 Embodiment # Disease, Vectors for CAR-T cell modification ailment or ut ke ut ke rectal tumors mRNA, shRNA, siRNA, saRNA, SeekRNA, polymers, proteins and peptides, antibodies, viruses, including but e ke epithelial tumor ut e ke ovarian tumors ut e ke breast tumors mRNA, shRNA, siRNA, saRNA, SeekRNA, polymers, proteins and peptides, antibodies, viruses, including but e ke fallo tumo ut e ke endo tumo ut e ke pancreatic mRNA, shRNA, siRNA, saRNA, SeekRNA, polymers, tumors proteins and peptides, antibodies, viruses, including but e ke colorectal tumors ut e ke lung tumor ut e ke gastrointestinal mRNA, shRNA, siRNA, saRNA, SeekRNA, polymers, tumors proteins and peptides, antibodies, viruses, including but e ke mela ut e ke multi myel ut e ke acute mRNA, shRNA, siRNA, saRNA, SeekRNA, polymers, lymphoblastic proteins and peptides, antibodies, viruses, including but leuk e ke acut myel ut leuk e ke non- lymp ut e ke diffuse large b- mRNA, shRNA, siRNA, saRNA, SeekRNA, polymers, cell lymphoma proteins and peptides, antibodies, viruses, including but ke ut ke ut ke ut (AAV), labelling molecules, small molecules, Virus-like particles (VLP), transposon / transposase (sleeping ke ut ke ut ke sickle cell mRNA, shRNA, siRNA, saRNA, SeekRNA, polymers, disease proteins and peptides, antibodies, viruses, including but e ke lupu eryth ut e ke lupu ut e ke myasthenia mRNA, shRNA, siRNA, saRNA, SeekRNA, polymers, gravis proteins and peptides, antibodies, viruses, including but e ke autoimmun diseases ut e ke soft tissue sarcoma ut e ke osteosarcoma mRNA, shRNA, siRNA, saRNA, SeekRNA, polymers, proteins and peptides, antibodies, viruses, including but e ke hepa carci ut e ke graft host ut e ke 33 rheumatoid mRNA, shRNA, siRNA, saRNA, SeekRNA, polymers, arthritis proteins and peptides, antibodies, viruses, including but ke ut ke Table 2 Embodiment # Vector for CAR-T cell Diseases, ailments, or conditions , sickle cell disease, lupus erythematosus, lupus nephritis, myasthenia gravis, , , , , lupus nephritis, myasthenia gravis, autoimmune diseases, soft tissue sarcoma, , e , , e autoimmune diseases, soft tissue sarcoma, osteosarcoma, hepatocellular carcinoma, , , , , osteosarcoma, hepatocellular carcinoma, graft versus host disease, rheumatoid , , , , graft versus host disease, rheumatoid arthritis, and impairments related to renal , , , , arthritis, and impairments related to renal transplantation Adeno Associated Viru (AAV) , e , labelling molecules , e , transplantation small molecules solid tumors such as anal / rectal, epithelial, , e , , e , transposon / transposase solid tumors such as anal / rectal, epithelial, (sleeping beauty) ovarian, breast, fallopian tube, endometrial, e , transposon / transpos (TcBuster) , e , transposon / transpos (PiggyBac) ovarian, breast, fallopian tube, endometrial, pancreatic, colorectal, lung, and / or , , , , pancreatic, colorectal, lung, and / or gastrointestinal tumors; melanoma, multiple , , e , , gastrointestinal tumors; melanoma, multiple myeloma, acute lymphoblastic leukemia, , programmable addit site-specific targetin , elements (PASTE) e , CRISPR / Cas , e myeloma, acute lymphoblastic leukemia, acute myelocytic lymphoma, non-Hodgkin , , e , Embodiments 1 to 59 listed in Tables 1 and 2 do not only apply to modified CAR-T cells, but also to any other modified cell types that can be produced by the cell processing or modification system or subsystem. Accordingly, a “modified cell” as used herein is a cell that has been produced by the cell processing or modification system or subsystem by use of the vectors of embodiments 35 to 59 (Table 2). The modified cell is further provided for use in the treatment of a disease, ailment, or condition according to embodiments 1 to 34 (Table 1). In an embodiment, the modified cells are modified Chimeric Antigen Receptor Natural Killer (CAR-NK) cells. In a further embodiment, the modified cells are modified Chimeric Antigen Receptor Monocytes (CAR-M) cells. In another embodiment, the modified cells are modified Engineered T-Cell Receptor (TCR) cells. In a further embodiment, the modified cells are modified Engineered B- Cells. In another embodiment, the modified cells are modified Tumor Infiltrating Lymphocytes (TIL) cells. In a further embodiment, the modified cells are modified Induced Pluripotent Stem (iPSC) Cells. In another embodiment, the modified cells are modified Invariant Natural Killer T (iNKT) cells. In a further embodiment, the modified cells are modified Mesenchymal Stem (MSC) cells. In another embodiment, the modified cells are modified Dendritic Cells. In a further embodiment, the modified cells are modified Hematopoietic Stem Cells / Stem (CD34+) cells. The modified cells can be produced and administered in a variety of environments by the bedside cell processing or modification system, with the modified cells being produced using any one of the preceding vectors and being administered in any one of the preceding applications or therapeutic treatments. By way of example, the bedside cell processing or modification system can produce and / or administer modified cells within a patient treatment room / facility (inpatient or outpatient). The bedside cell processing or modification system can produce and / or administer modified cells within a cell processing lab. The cell processing lab may be at a hospital facility, at a non-hospital facility, or a commercial production facility (centralized or decentralized). The bedside cell processing or modification system can produce and / or administer modified cells within a sterile manufacturing suite. The sterile manufacturing suite may be at a hospital facility, at a non-hospital facility, at an academic facility, or at commercial production facility (centralized or decentralized). While the modified cells produced by this system are described as being used to treat particular conditions and patient groups, it should be understood that they may be applied to other conditions and / or patient groups, including sub- groups of a described patient group (i.e., patients having the same characteristics that characterize a particular patient group, but additional characteristics that are not shared by all patients of that patient group), larger patient groups encompassing a described patient group (i.e., a patient group having broadly defined characteristics that include the characteristics that characterize a particular patient group) and entirely different patient groups (i.e., patients having characteristics that exclude them from a particular patient group). The modified cells may also be applied in various dosages, administrative regimes, and routes of administration without departing from the scope of the present disclosure. It should be understood that the embodiments disclosed herein may be combined with each other in any imaginable combination. Aspects Aspect 1. Modified cells for use in the treatment of a disease, ailment, or medical condition of a patient, characterized in that the modified cells are produced using a bedside cell modification system, comprising: an apheresis system configured to collect from the patient a blood component comprising target cells; a cell modification subsystem configured to receive the target cells from the apheresis system and to modify the target cells; and a reinfusion system configured to receive the modified target cells from the cell modification subsystem and to return the modified cells to the patient so as to treat the disease, ailment, or medical condition of the patient. Aspect 2. The modified cells of Aspect 1, wherein the target cells are selected from the group consisting of chimeric antigen receptor T-cells, chimeric antigen receptor natural killer cells, chimeric antigen receptor monocyte cells, engineered T-cell receptors, engineered B-cells, tumor infiltrating lymphocytes, induced pluripotent stem cells, mesenchymal stem cells, dendritic cells, and hematopoietic stem cells. Aspect 3. The modified cells of any one of the preceding Aspects, wherein the target cells are modified using a vector selected from the group consisting of lentivirus, adeno associated virus, virus-like particles, transposon / transposase, transcription activator-like effector nuclease, zinc finger nucleases, mRNA, shRNA, siRNA, SeekRNA, CRISPR / Cas, base editors, prime editors, and programmable addition via site-specific targeting elements. Aspect 4. The modified cells of any one of the preceding Aspects, wherein the modified cells are produced in an environment selected from the group consisting of a patient treatment room of an inpatient facility, a patient treatment room of an outpatient facility, a cell processing lab of a hospital facility, a cell processing lab of a non-hospital facility, a cell processing lab of a centralized commercial production facility, a cell processing lab of a decentralized commercial production facility, a sterile manufacturing suite of a hospital facility, a sterile manufacturing suite of a non-hospital facility, a sterile manufacturing suite of an academic facility, a sterile manufacturing suite of a centralized commercial production facility, and a sterile manufacturing suite of a decentralized commercial production facility. Aspect 5. The modified cells of any one of the preceding Aspects, wherein said disease, ailment, or medical condition is selected from the group consisting of solid tumors, melanoma, multiple myeloma, acute lymphoblastic leukemia, acute myelocytic leukemia, non-Hodgkin lymphoma, diffuse large B-cell lymphoma, small-cell lung cancer, renal transplantation, neuroblastoma, glioblastoma, prostate cancer, hemophilia, sickle cell disease, lupus erythematosus, lupus nephritis, myasthenia gravis, autoimmune diseases, soft tissue sarcoma, osteosarcoma, hepatocellular carcinoma, graft versus host disease, and rheumatoid arthritis. Aspect 6. Modified cells for use in the treatment of a disease, ailment, or medical condition of a patient, characterized in that the modified cells are produced at bedside using a method comprising: connecting an apheresis system to the patient via a collection flow path; connecting the apheresis system to a cell modification subsystem via a collected target cells flow path; connecting the cell modification subsystem to a reinfusion system via a modified target cells flow path; connecting the reinfusion system to the patient via a reinfusion system flow path; operating the apheresis system to collect from the patient via the collection flow path a blood component comprising target cells; operating the cell modification subsystem to receive the target cells from the apheresis system via the collected target cells flow path and to modify the target cells; and operating the reinfusion system to receive the modified target cells from the cell modification subsystem via the modified target cells flow path and to return the modified target cells to the patient via the reinfusion system flow path so as to treat the disease, ailment, or medical condition of the patient. Aspect 7. The modified cells of Aspect 6, wherein the target cells are selected from the group consisting of chimeric antigen receptor T-cells, chimeric antigen receptor natural killer cells, chimeric antigen receptor monocyte cells, engineered T-cell receptors, engineered B-cells, tumor infiltrating lymphocytes, induced pluripotent stem cells, mesenchymal stem cells, dendritic cells, and hematopoietic stem cells. Aspect 8. The modified cells of any one of Aspects 6-7, wherein the target cells are modified using a vector selected from the group consisting of lentivirus, adeno associated virus, virus-like particles, transposon / transposase, transcription activator-like effector nuclease, zinc finger nucleases, mRNA, shRNA, siRNA, SeekRNA, CRISPR / Cas, base editors, prime editors, and programmable addition via site-specific targeting elements. Aspect 9. The modified cells of any one of Aspects 6-8, wherein the modified cells are produced in an environment selected from the group consisting of a patient treatment room of an inpatient facility, a patient treatment room of an outpatient facility, a cell processing lab of a hospital facility, a cell processing lab of a non-hospital facility, a cell processing lab of a centralized commercial production facility, a cell processing lab of a decentralized commercial production facility, a sterile manufacturing suite of a hospital facility, a sterile manufacturing suite of a non-hospital facility, a sterile manufacturing suite of an academic facility, a sterile manufacturing suite of a centralized commercial production facility, and a sterile manufacturing suite of a decentralized commercial production facility. Aspect 10. The modified cells of any one of Aspects 6-9, wherein said disease, ailment, or medical condition is selected from the group consisting of solid tumors, melanoma, multiple myeloma, acute lymphoblastic leukemia, acute myelocytic leukemia, non-Hodgkin lymphoma, diffuse large B-cell lymphoma, small-cell lung cancer, renal transplantation, neuroblastoma, glioblastoma, prostate cancer, hemophilia, sickle cell disease, lupus erythematosus, lupus nephritis, myasthenia gravis, autoimmune diseases, soft tissue sarcoma, osteosarcoma, hepatocellular carcinoma, graft versus host disease, and rheumatoid arthritis. It will be understood that the embodiments described above are illustrative of some of the applications of the principles of the present subject matter. Numerous modifications may be made by those skilled in the art without departing from the spirit and scope of the claimed subject matter, including those combinations of features that are individually disclosed or claimed herein. For these reasons, the scope hereof is not limited to the above description but is as set forth in the following claims, and it is understood that claims may be directed to the features hereof, including as combinations of features that are individually disclosed or claimed herein.

Claims

CLAIMS 1. Modified cells for use in the treatment of a disease, ailment, or medical condition of a patient, characterized in that the modified cells are produced using a bedside cell modification system, comprising: an apheresis system configured to collect from the patient a blood component comprising target cells; a cell modification subsystem configured to receive the target cells from the apheresis system and to modify the target cells; and a reinfusion system configured to receive the modified target cells from the cell modification subsystem and to return the modified cells to the patient so as to treat the disease, ailment, or medical condition of the patient.

2. The modified cells of claim 1, wherein the target cells are selected from the group consisting of chimeric antigen receptor T-cells, chimeric antigen receptor natural killer cells, chimeric antigen receptor monocyte cells, engineered T-cell receptors, engineered B-cells, tumor infiltrating lymphocytes, induced pluripotent stem cells, mesenchymal stem cells, dendritic cells, and hematopoietic stem cells.

3. The modified cells of any one of the preceding claims, wherein the target cells are modified using a vector selected from the group consisting of lentivirus, adeno associated virus, virus-like particles, transposon / transposase, transcription activator-like effector nuclease, zinc finger nucleases, mRNA, shRNA, siRNA, SeekRNA, CRISPR / Cas, base editors, prime editors, and programmable addition via site-specific targeting elements.

4. The modified cells of any one of the preceding claims, wherein the modified cells are produced in an environment selected from the group consisting of a patient treatment room of an inpatient facility, a patient treatment room of an outpatient facility, a cell processing lab of a hospital facility, a cell processing lab of a non-hospital facility, a cell processing lab of a centralized commercial production facility, a cell processing lab of a decentralized commercial production facility, a sterile manufacturing suite of a hospital facility, a sterile manufacturingsuite of a non-hospital facility, a sterile manufacturing suite of an academic facility, a sterile manufacturing suite of a centralized commercial production facility, and a sterile manufacturing suite of a decentralized commercial production facility.

5. The modified cells of any one of the preceding claims, wherein said disease, ailment, or medical condition is selected from the group consisting of solid tumors, melanoma, multiple myeloma, acute lymphoblastic leukemia, acute myelocytic leukemia, non-Hodgkin lymphoma, diffuse large B-cell lymphoma, small-cell lung cancer, renal transplantation, neuroblastoma, glioblastoma, prostate cancer, hemophilia, sickle cell disease, lupus erythematosus, lupus nephritis, myasthenia gravis, autoimmune diseases, soft tissue sarcoma, osteosarcoma, hepatocellular carcinoma, graft versus host disease, and rheumatoid arthritis.

6. Modified cells for use in the treatment of a disease, ailment, or medical condition of a patient, characterized in that the modified cells are produced at bedside using a method comprising: connecting an apheresis system to the patient via a collection flow path; connecting the apheresis system to a cell modification subsystem via a collected target cells flow path; connecting the cell modification subsystem to a reinfusion system via a modified target cells flow path; connecting the reinfusion system to the patient via a reinfusion system flow path; operating the apheresis system to collect from the patient via the collection flow path a blood component comprising target cells; operating the cell modification subsystem to receive the target cells from the apheresis system via the collected target cells flow path and to modify the target cells; and operating the reinfusion system to receive the modified target cells from the cell modification subsystem via the modified target cells flow path and to return the modified target cells to the patient via the reinfusion system flow path so as to treat the disease, ailment, or medical condition of the patient.

7. The modified cells of claim 6, wherein the target cells are selected from the group consisting of chimeric antigen receptor T-cells, chimeric antigen receptor natural killer cells, chimeric antigen receptor monocyte cells, engineered T-cell receptors, engineered B-cells, tumor infiltrating lymphocytes, induced pluripotent stem cells, mesenchymal stem cells, dendritic cells, and hematopoietic stem cells.

8. The modified cells of any one of claims 6-7, wherein the target cells are modified using a vector selected from the group consisting of lentivirus, adeno associated virus, virus-like particles, transposon / transposase, transcription activator-like effector nuclease, zinc finger nucleases, mRNA, shRNA, siRNA, SeekRNA, CRISPR / Cas, base editors, prime editors, and programmable addition via site-specific targeting elements.

9. The modified cells of any one of claims 6-8, wherein the modified cells are produced in an environment selected from the group consisting of a patient treatment room of an inpatient facility, a patient treatment room of an outpatient facility, a cell processing lab of a hospital facility, a cell processing lab of a non- hospital facility, a cell processing lab of a centralized commercial production facility, a cell processing lab of a decentralized commercial production facility, a sterile manufacturing suite of a hospital facility, a sterile manufacturing suite of a non-hospital facility, a sterile manufacturing suite of an academic facility, a sterile manufacturing suite of a centralized commercial production facility, and a sterile manufacturing suite of a decentralized commercial production facility.

10. The modified cells of any one of claims 6-9, wherein said disease, ailment, or medical condition is selected from the group consisting of solid tumors, melanoma, multiple myeloma, acute lymphoblastic leukemia, acute myelocytic leukemia, non-Hodgkin lymphoma, diffuse large B-cell lymphoma, small-cell lung cancer, renal transplantation, neuroblastoma, glioblastoma, prostate cancer, hemophilia, sickle cell disease, lupus erythematosus, lupus nephritis, myasthenia gravis, autoimmune diseases, soft tissue sarcoma, osteosarcoma, hepatocellular carcinoma, graft versus host disease, and rheumatoid arthritis.

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