Cell Therapy and Therapy Reinfusion Methods

Abstract

Tumor tissue, including soft and / or bone tissue, is harvested from a subject and morselized. The morselized tissue is placed in a cartridge, which is placed in a storage chamber of a tumor tissue processing device. Cancer cells within the morselized tumor tissue are destroyed without destroying tumor antigens therein. These cells are cryogenically destroyed by exposing the cartridge to a cooling fluid such as liquid nitrogen, optionally using a warming cycle, and optionally using more than one freeze / thaw cycle. The treated tissue and / or cells are then extracted from the cartridge and reintroduced into the subject after they reach a threshold condition. The treated tissue and / or cells can be reintroduced via a storage sleeve or a reimplantation bag.

Description

[Background technology]

[0001] (cross reference) This PCT application claims priority to U.S. Provisional Application No. 62 / 877,011, filed July 22, 2019, which is incorporated by reference in its entirety.

[0002] (background) Cancer is a leading cause of death in the United States, other countries, and the world. Traditionally, cancer is treated using surgery, chemotherapy, radiation therapy, or a combination thereof. In recent years, immunotherapy-based approaches have gained success and traction. These include monoclonal antibodies, non-specific immunotherapy, oncolytic virotherapy, T-cell therapy such as chimeric antigen receptor (CAR) T-cell therapy, and tumor antigen vaccines. The effectiveness of these therapies is primarily due to the personalization of these therapies to target patients. Despite significant progress, a "cure" for cancer has yet to be realized, and improvements to cancer therapy remain desirable.

[0003] Relevant publications include US20190023670, US20180362519, US20180044630, US20140227781, US20130122049, and US6036681. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] U.S. Patent Application Publication No. 2019 / 0023670 [Patent Document 2] U.S. Patent Application Publication No. 2018 / 0362519 Summary of the Invention [Problem to be solved by the invention]

[0005] (summary) The present disclosure provides methods, systems, and devices for treating tissues and / or cells extracted from a subject for subsequent therapeutic infusion back into the subject, often as a tumor antigen vaccine to treat cancer. [Means for solving the problem]

[0006] Aspects of the present disclosure provide methods for treating tissue or cells for therapy reinfusion. Tumor tissue, including soft and / or bony tissue, may be harvested from a subject. The tumor tissue may be generally morcellated within a storage chamber or a specific morcellation device. Cancer cells within the morcellated tumor tissue may be destroyed or otherwise inactivated without destroying tumor antigens therein. The cancer cells may be destroyed by cooling (e.g., cryogenically) with liquid nitrogen or the like. This cell inactivation or destruction may be enhanced by one or more freeze / thaw cycles, which may be further optimized by adjusting the rate of cooling and warming within the freeze / thaw cycle and / or the length, number, and / or pattern of the freeze / thaw cycles. The freeze / thaw cycles may be implemented in conjunction with a storage chamber that houses the morcellated tissue. The tumor tissue, with its inactivated or destroyed cancer cells and preserved antigens, may then be extracted from the storage chamber and reintroduced into the subject. The tissue may be extracted only upon reaching a threshold condition, such as a threshold temperature or immersion level in a processing chamber and / or a number of freeze / thaw cycles of a defined length and / or pattern. In some cases, the tissue is reintroduced with a containment element, such as a sleeve, which may be optimized to enhance the immune response to the reimplanted tissue.

[0007] Aspects of the present disclosure also provide systems and devices for treating tissue or cells for therapy reinfusion. Exemplary systems may include a housing including a cartridge for storing and processing harvested tumor tissue, a tissue morsel within the cartridge, operably coupled to the cartridge, or operated independently of the cartridge, a storage chamber for removably holding the cartridge, and, optionally, a drive for the tissue morsel; a cooling fluid port fluidly coupled to the storage chamber for introducing a coolant into the storage chamber to cool the cartridge; and / or a user interface for one or more of: (i) displaying one or more of the time, temperature within the storage chamber, and / or morsel status; (ii) controlling one or more of the timer, temperature, and / or drive for the tissue morsel; and / or (iii) monitoring and driving characteristics of one or more freeze / thaw cycles. These characteristics may include the rate and duration of freezing, the rate and duration of thawing, target temperatures for freezing and thawing, etc. The system may further include a heated air or fluid port fluidly coupled to the storage chamber for the introduction of heated air or fluid into the storage chamber to warm or melt the cartridge. Alternatively, or in combination, a heating element, such as an induction and / or resistance heating element, may be provided to warm or melt the cartridge. The cartridge may be in the form of a tube, tray, and / or mesh cylinder.

[0008] Aspects of the present disclosure provide methods for treating cancer. An exemplary method may include reintroducing tumor tissue removed from a subject into the subject, the reintroduced tumor tissue having cancer cells that are inactivated without destroying tumor antigens in the cancer cells.

[0009] The tumor tissue harvested from the subject may include one or more of soft tissue or bone tissue. The method may further include harvesting the tumor tissue from the subject. The method may further include morselizing the harvested tumor tissue from the subject prior to reintroducing the tumor tissue into the subject. The tumor tissue may be morselized by placing the harvested tumor tissue in a storage chamber, where the tumor tissue is morselized.

[0010] The method may further include a step of inactivating cancer cells in tumor tissue removed from the subject. Inactivating cancer cells in tumor tissue may include destroying the cancer cells. Inactivating cancer cells in tumor tissue may include cooling the tumor tissue. The tumor tissue may be cooled after being morselized. The cooled tumor tissue may be warmed. The method may further include a step of repeating one or more cooling and warming cycles on the tumor tissue. The one or more cooling and warming cycles may conform to a defined range of cooling and warming rates optimized to inactivate or kill the cells without destroying tumor antigens. The tumor tissue with the inactivated cancer cells may be reintroduced into the subject after the tumor tissue has reached a threshold number of cooling and warming cycles and / or after the tumor tissue has reached a threshold temperature, optionally for a predetermined period of time. The tumor tissue may be cooled by cryogenically treating the tumor tissue with liquid nitrogen, etc. The inactivated tumor tissue with its cancer cells may be reintroduced with a storage element, such as a storage sleeve.

[0011] Aspects of the present disclosure provide a system for treating tissue or cells for therapy reinfusion. An exemplary system includes a housing including a cartridge and a storage chamber for removably holding the cartridge for storing and processing harvested tumor tissue;

[0012] A cooling fluid port fluidly coupled to the storage chamber for introduction of a coolant into the storage chamber to cool the cartridge may be included, and a user interface may be configured for one or more of (i) displaying the time, the temperature in the storage chamber, or the phase of the freeze / thaw cycle, (ii) controlling the timer or the temperature in the storage chamber, or (iii) monitoring and driving one or more freeze / thaw cycle characteristics.

[0013] The system may further include a tissue morsel within the cartridge. The housing may include a drive for the tissue morsel. The user interface may be configured to display a morsel status of the harvested tumor tissue. The user interface may be configured to control the drive for the tissue morsel.

[0014] The system may further include a heated air port fluidly coupled to the storage chamber for introducing heated air into the storage chamber to warm or melt the cartridge.

[0015] The cartridge may be in a variety of forms, such as a tube, tray, mesh cylinder, or the like. The present invention provides, for example, the following. (Item 1) 1. A method for treating cancer, said method comprising: 1. A method comprising reintroducing tumor tissue removed from a subject into the subject, the reintroduced tumor tissue having cancer cells thereof that are inactivated without destroying tumor antigens in the cancer cells. (Item 2) 2. The method of claim 1, wherein the tumor tissue collected from the subject comprises one or more of soft tissue or bone tissue. (Item 3) 2. The method of claim 1, further comprising harvesting the tumor tissue from the subject. (Item 4) 10. The method of claim 1, further comprising morcellating the tumor tissue removed from the subject prior to reintroducing the tumor tissue into the subject. (Item 5) 5. The method of claim 4, wherein morcellating the tumor tissue comprises placing the harvested tumor tissue in a storage chamber, and the tumor tissue is morcellated in the storage chamber. (Item 6) 2. The method of claim 1, further comprising inactivating cancer cells in the tumor tissue removed from the subject. (Item 7) 7. The method according to item 6, wherein inactivating cancer cells in the tumor tissue comprises destroying the cancer cells. (Item 8) 7. The method of claim 6, wherein inactivating cancer cells in the tumor tissue comprises cooling the tumor tissue. (Item 9) 9. The method of claim 8, wherein the tumor tissue is cooled after being morselized. (Item 10) 9. The method of claim 8, further comprising warming the cooled tumor tissue. (Item 11) 11. The method of claim 10, further comprising repeating one or more cooling and heating cycles on the tumor tissue. (Item 12) 12. The method of claim 11, wherein the one or more cooling and heating cycles conform to a defined range of cooling and heating rates that is optimized to inactivate or kill cells without destroying tumor antigens. (Item 13) 12. The method of claim 11, wherein the tumor tissue with the inactivated cancer cells is reintroduced into the subject after the tumor tissue has reached a threshold number of cooling and warming cycles. (Item 14) 9. The method of claim 8, wherein the tumor tissue with the inactivated cancer cells is reintroduced into the subject after the tumor tissue has reached a threshold temperature. (Item 15) 14. The method of claim 13, wherein the tumor tissue with the inactivated cancer cells is reintroduced into the subject after the tumor tissue has reached the threshold temperature for a predetermined period of time. (Item 16) 9. The method of claim 8, wherein cooling the tumor tissue comprises treating the tumor tissue with cryogenic temperatures. (Item 17) 17. The method of claim 16, wherein the tumor tissue is cryogenically treated using liquid nitrogen. (Item 18) 2. The method of claim 1, wherein the tumor tissue with the cancer cells thereof that has been deactivated is reintroduced together with a storage element. (Item 19) Item 19. The method of item 18, wherein the storage element comprises a storage sleeve. (Item 20) 1. A system for treating tissue or cells for therapeutic reinfusion, the system comprising: a cartridge for storing and processing the harvested tumor tissue; a housing including a storage chamber for removably holding the cartridge; a cooling fluid port fluidly coupled to the storage chamber for introduction of a coolant into the storage chamber to cool the cartridge; (i) displaying one or more of the time, the temperature within said storage chamber, or the phase of a freeze / thaw cycle; or (ii) controlling one or more of a timer or the temperature within the storage chamber; or (iii) monitoring and driving one or more freeze / thaw cycle characteristics; a user interface for one or more of A system comprising: (Item 21) 21. The system of claim 20, further comprising a tissue morsel within the cartridge, the housing including a drive for the tissue morsel. (Item 22) 22. The system of claim 21, wherein the user interface is configured to display a morcellation status of the harvested tumor tissue. (Item 23) 22. The system of claim 21, wherein the user interface is configured to control the drive for the tissue morsel. (Item 24) 21. The system of claim 20, further comprising a heated air port fluidly coupled to the storage chamber for introducing heated air into the storage chamber to warm or melt the cartridge. (Item 25) 21. The system of claim 20, wherein the cartridge comprises a tube. (Item 26) 21. The system of claim 20, wherein the cartridge comprises a tray. (Item 27) 21. The system of claim 20, wherein the cartridge comprises a mesh cylinder.

[0016] (Incorporated by reference) All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. [Brief explanation of the drawings]

[0017] The novel features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings.

[0018] [Figure 1A] FIG. 1A is a schematic diagram of a tumor tissue processing device according to an embodiment of the present disclosure.

[0019] [Figure 1B] FIG. 1B is a top view of the storage chamber of the tumor tissue processing device of FIG. 1A.

[0020] [Figure 2] FIG. 2 is a side view of an exemplary storage chamber for a tumor tissue processing device according to an embodiment of the present disclosure.

[0021] [Figure 3] FIG. 3 is a flowchart of a method for processing and reinjecting tumor tissue according to an embodiment of the present disclosure.

[0022] [Figure 4A] FIG. 4A shows a perspective view of a tissue processing system according to an embodiment of the present disclosure.

[0023] [Figure 4B] FIG. 4B shows an exploded view of the tissue processing system of FIG. 4A.

[0024] [Figure 4C] 4C, 4D, and 4E show a perspective view, a (left) side view, and a (right) side view, respectively, of the console shell of the tissue processing system of FIG. 4A. [Figure 4D] 4C, 4D, and 4E show a perspective view, a (left) side view, and a (right) side view, respectively, of the console shell of the tissue processing system of FIG. 4A. [Figure 4E] 4C, 4D, and 4E show a perspective view, a (left) side view, and a (right) side view, respectively, of the console shell of the tissue processing system of FIG. 4A.

[0025] [Figure 4F] 4F and 4G show perspective views of the multi-purpose lid of the tissue processing system of FIG. 4A. [Figure 4G] 4F and 4G show perspective views of the multi-purpose lid of the tissue processing system of FIG. 4A.

[0026] [Figure 4H] FIG. 4H shows a perspective view of the lid lock of the tissue processing system of FIG. 4A.

[0027] [Figure 4I] 4I, 4J, and 4K show perspective views of the tissue processing system of FIG. 4A in the cryogenic / cooling cycle position, the transition position, and the warming cycle position, respectively. [Figure 4J]4I, 4J, and 4K show perspective views of the tissue processing system of FIG. 4A in the cryogenic / cooling cycle position, the transition position, and the warming cycle position, respectively. [Figure 4K] 4I, 4J, and 4K show perspective views of the tissue processing system of FIG. 4A in the cryogenic / cooling cycle position, the transition position, and the warming cycle position, respectively.

[0028] [Figure 4L] FIG. 4L shows a flowchart of an exemplary method of using the tissue processing system of FIG. 4A, according to an embodiment of the present disclosure.

[0029] [Figure 5A] FIG. 5A shows a perspective view of a tissue processing system according to a further embodiment of the present disclosure.

[0030] [Figure 5B] FIG. 5B shows a front view of the tissue processing system of FIG. 5A.

[0031] [Figure 5C] FIG. 5C shows a top view of the conversion chamber of the tissue processing system of FIG. 5A.

[0032] [Figure 5D] 5D, 5E, and 5F show side cross-sectional views of the conversion chamber of the tissue processing system of FIG. 5A in the cryogenic / cooling cycle position, the transition position, and the warming cycle position, respectively. [Figure 5E] 5D, 5E, and 5F show side cross-sectional views of the conversion chamber of the tissue processing system of FIG. 5A in the cryogenic / cooling cycle position, the transition position, and the warming cycle position, respectively. [Figure 5F] 5D, 5E, and 5F show side cross-sectional views of the conversion chamber of the tissue processing system of FIG. 5A in the cryogenic / cooling cycle position, the transition position, and the warming cycle position, respectively.

[0033] [Figure 5G]FIG. 5G shows a bottom perspective view of the uncoated transduction chamber of the tissue processing system of FIG. 5A.

[0034] [Figure 5H] 5H and 5I show perspective and side views, respectively, of a tissue tray for the conversion chamber of the tissue processing system of FIG. 5A. [Figure 5I] 5H and 5I show perspective and side views, respectively, of a tissue tray for the conversion chamber of the tissue processing system of FIG. 5A.

[0035] [Figure 5J] FIG. 5J shows a perspective view of a cover for the conversion chamber of the tissue processing system of FIG. 5A.

[0036] [Figure 5K] FIG. 5K shows a flowchart of an exemplary method of using the tissue processing system of FIG. 5A, according to an embodiment of the present disclosure.

[0037] [Figure 6A] 6A and 6B show a perspective view and a side view, respectively, of a tissue processing system according to a further embodiment of the present disclosure. [Figure 6B] 6A and 6B show a perspective view and a side view, respectively, of a tissue processing system according to a further embodiment of the present disclosure.

[0038] [Figure 6C] 6C and 6D show side cross-sectional views of the tissue processing system of FIGS. 6A and 6B in the "cold gas on" and "cold gas off" positions, respectively. [Figure 6D] 6C and 6D show side cross-sectional views of the tissue processing system of FIGS. 6A and 6B in the "cold gas on" and "cold gas off" positions, respectively.

[0039] [Figure 6E]6E and 6F show perspective and side views, respectively, of a mesh assembly for holding tissue to be processed for the tissue processing system of FIGS. 6A and 6B according to an embodiment of the present disclosure. [Figure 6F] 6E and 6F show perspective and side views, respectively, of a mesh assembly for holding tissue to be processed for the tissue processing system of FIGS. 6A and 6B according to an embodiment of the present disclosure.

[0040] [Figure 6G] FIG. 6G shows a perspective view of a ring tissue / bone obturator suitable for use with the mesh assembly of FIGS. 6E and 6F, according to an embodiment of the present disclosure.

[0041] [Figure 6H] FIG. 6H shows a perspective view of the mesh assembly of 6E and 6F, uncoated.

[0042] [Figure 6I] FIG. 6I shows a perspective view of the ring tissue / bone obturator of FIG. 6G in combination with the mesh assembly of FIGS. 6A and 6B.

[0043] [Figure 6J] FIG. 6J shows a flowchart of an exemplary method of using the tissue processing system of FIGS. 6A and 6B, according to an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0044] (Detailed explanation) The present disclosure provides methods, systems, and devices for treating tissues and / or cells extracted from a subject for subsequent therapeutic infusion back into the subject, often as a tumor antigen vaccine to treat cancer. In particular, provided are devices configured to kill tumor cells while preserving tumor antigens to allow for re-implantation (also referred to herein as "re-infusion" or "reintroduction") of the killed tumor cells into the patient to stimulate an immune response to the tumor.

[0045] A suitable tumor tissue processing device should fulfill many device requirements. The device should predictably prepare the tissue through the steps of the tissue processing method to kill tumor cells, which will often include cryogenic treatment, optionally with one or more freeze / thaw cycles. The device should facilitate cryogenic treatment of tumor tissue in a predictable manner to allow complete freezing of the tissue followed by cell lysis, resulting in destruction of cell viability. The device should be capable of delivering the resulting tissue for reimplantation or reinfusion. The device may have an implantation cuff for ease of storage and reimplantation or reinfusion of tumor tissue.

[0046] Many of the key elements of a tumor tissue processing device are shown in FIG. 1A, which shows an exemplary tumor tissue processing device 100. A key component is the storage chamber 110, which can interface with a replaceable cartridge for tissue morsel, tissue storage, and / or other processing. Harvested tumor tissue may be placed into the cartridge, within which the tumor tissue treatment phases can be performed. The tumor tissue can therefore remain within the cartridge throughout the entire treatment, ensuring complete treatment without contamination of untreated tissue. Typically, the tissue never exits the cartridge until treatment is completed, but in some cases, the tissue may be morselized using a separate device and placed within the cartridge throughout the treatment, including cooling and warming cycles. Two types of cartridges may be provided: one for bone and hard tissue, and one for soft tissue.

[0047] In some embodiments, tissue is morselized within the same cartridge as the one for downstream (cooling and warming) treatment. The bone / hard tissue cartridge may have a mechanical blade 130, as shown in FIG. 1B, that pivots and breaks the tissue into smaller pieces that can be predictably treated with liquid nitrogen or other cryogenic / cooling fluid. Piece size can be determined by laboratory testing that considers the depth of cryogenic treatment penetration (typically with liquid nitrogen, as introduced by a funnel 140, as shown in FIG. 1A) over a period of time to ensure complete treatment. The blade 130 can interact with a drill 150 within the upper portion of the device 100, which pivots the blade 130 for the required amount of time.

[0048] The soft tissue cartridge can have a series of sharp sieves that not only cut the tissue to the required size, again based on temperature penetration testing, but also into smaller pieces for easier handling due to handling requirements. These sharp sieves can be activated by a mechanical lever 150 that is depressed by the clinician or is automated to initiate the functioning of the device.

[0049] The tumor tissue processing device may have a first portion for allowing the initial device function to operate, i.e., for the cartridge to be placed into the device and then for the tissue morsel function to be performed with the aid of the cartridge (e.g., initial storage chamber 120a as shown in FIG. 2). The tumor tissue processing device may include a lever or plunger 150 (e.g., in the form of a top / front plate) that can be unfolded and move the cartridge into a second portion of the device 100 that immerses the cartridge in liquid nitrogen (or some other coolant), and then is fully immersed for the required time (e.g., final storage chamber 120b as shown in FIG. 2). As shown in FIG. 1A, there may be a timer 160 on the device 100 that produces a visual and / or audible signal when treatment is being performed. As shown in FIG. 1A, the device 100 may also have a temperature readout 170 (as measured by sensor 180, which may measure temperature and other conditions such as pH, oxygenation, moisture content, etc.) and a readout for the number of freeze / heat cycles. The coolant can then be drained from the device's tissue storage chamber (suction / gravity port 190 for drainage, as shown in FIG. 1B) to minimize the likelihood of burning the clinician, and a cartridge can then be delivered from the device to allow for re-implantation or re-infusion of the tissue. Optionally, the device may facilitate one or more freeze / thaw cycles of defined characteristics. Optionally, the tumor tissue can then be delivered into an implantable bag to facilitate re-implantation. The re-implantation bag can be composed of either absorbable or non-absorbable material to allow for easy explantation. The material may be optimized to enhance or potentiate the immune response to the re-implanted tissue. The bag may be porous to allow for easy bioavailability, which is often important for stimulating an immune response. A bag or sleeve may be fitted over the top of the storage chamber after the top of the chamber is removed or opened.The device may also include a cartridge temperature monitor to confirm that proper temperature cycling has been achieved not only to kill tumor cells but also to allow the clinician to know when the temperature has returned to room temperature to allow for safe handling and re-implantation.

[0050] FIG. 3 shows a flowchart of a tumor tissue processing and reinfusion method 300. Tumor tissue may first be harvested, for example, in step 310. The tumor tissue may be bone tissue, soft tissue, or both. The harvested tumor tissue may then be placed in a storage chamber, typically a cartridge, for example, in step 320. The tumor tissue may then be morselized, for example, in step 330. The tumor tissue may then be treated, for example, with a cryogenic agent, such as liquid nitrogen, to kill or otherwise inactivate cells without destroying their tumor antigens, for example, in step 340. The tumor tissue may be cooled to a temperature of −50° C. or below to kill, destroy, or otherwise inactivate cancerous cells within the morselized tissue. The temperature and / or immersion level of the treated tissue can be monitored, and once a threshold temperature, such as at or below -50°C, is reached for at least a given period of time, such as one minute, the treated tissue may be thawed (i.e., heated or warmed) in step 350. Once a threshold temperature, such as at or below -50°C, is again reached for at least a given period of time, such as one minute, the treated tissue may be cooled again. After one or more of the freezing / heating cycles or repeating steps 340 and 350 in step 360, the treated tissue may be collected. In some embodiments, repeated cooling and heating may not be necessary. In step 370, the treated tissue can be removed from the cartridge and tissue treatment system. The treated tissue can then be reimplanted, for example, in step 380. The treated tissue is typically reimplanted in a tissue containment sleeve or bag, but can also be reimplanted alone. One use may be for bone grafting in fusion procedures.

[0051] While the above steps describe a particular method of harvesting, processing, and reintroducing tissue according to many embodiments, those skilled in the art will recognize many variations based on the teachings described herein. Steps may be completed in a different order. Steps may be added or omitted. Some of the steps may include sub-steps. Many of the steps may be repeated as many times as is beneficial to the treatment.

[0052] 4A-4M, a tissue processing system 400 and an exemplary method of use 4000 for the system 400 are described. The tissue processing system 400 may include a conversion chamber console 410, a lid 420, and a carousel 430 for tubes 432 for holding morselized tissue, as shown in FIG. 4B. Alternatively, or in combination with the use of the carousel 430 with tubes 432 for holding morselized tissue, a mesh assembly as described herein, for example, a mesh assembly described further below with reference to FIGS. 6A-6J, may be used. The chamber console 410 may include a power button 412 and a user interface 414, which may include a graphic display, as shown in FIG. 4A. The system 400 may further include a lid cover 422 operably coupleable to the lid 420. The chamber console 410 may include a console shell 416 and may define a conversion chamber 440 and a (cooling / warming) cycle switch 450. 4C-4E, the console shell 416 may define a cavity 460. The cavity 460 may house a cryogenic or cooling gas delivery system on one side and a warming air delivery system on the other side, as well as electronic control components of the system 400. The system 400 may further include a cryogenic or cooling gas inlet 470 and a melting and / or warming air inlet 480.

[0053] Lid 420 may be a multi-purpose lid and have multiple purposes, including closing conversion chamber 440, switching system 400 between cryogenic / cooling and warming / thawing cycles, allowing either cryogenic / cooled gas or warmed air to enter the conversion chamber, and / or providing ventilation. As shown in FIGS. 4F and 4G, lid 420 may include a vent 424, a cryogenic or cooled gas inlet 426 that may be aligned with cryogenic gas inlet 470, and a warmed gas inlet 428 that may be aligned with warmed gas inlet 480. As shown in FIG. 4H, lid lock 422 may include a wedge-shaped shaft 423 and an opening 425 that may be aligned with vent 424 of lid 420 in the (vent) open position. Lid 420 may be rotated relative to lid lock 422 (in a relatively steady state) to open and close vent 424. Wedge-shaped shaft 423 can orient window or opening 425 to allow predictable opening and closing of lid 424 as it is actuated. Lid lock 422 may be held in place by a magnet, such as a rare earth magnet, in the bottom of conversion chamber 440.

[0054] As shown in FIGS. 4I-4K, the lid 420 may be rotated to open and close the vents 424, 425 and interface with a cycle switch 450 to switch the system 400 between a cooling function and a warming / thawing function. The lid 420 may be positioned in a cryogenic or cooling cycle position 450c with the vent 424 closed, as in FIG. 4AI. While the vent 424 is closed, the vent 424 is not completely sealed, in some embodiments, such that there is little to no pressure buildup. In the cryogenic or cooling cycle position 450c, the cryogenic gas inlet 426 of the lid 420 may be aligned with the cryogenic gas inlet 470, allowing cryogenic or cooling gas to enter the conversion chamber 440, as in FIG. 4F, while the warming gas inlet 428 may be misaligned with the warming gas inlet 480, preventing the warming gas from entering the conversion chamber 440.

[0055] The lid 420 may be positioned in a transition position with the lid with vent 424 partially open, as in FIG. 4J. In this transition position, the cryogenic gas inlet 426 of the lid 420 may be misaligned with the cryogenic gas inlet 470 to prevent cryogenic or cooling gas from entering the conversion chamber 440, and the warm gas inlet 428 may be misaligned with the warm gas inlet 480 to prevent warm gas from entering the conversion chamber 440.

[0056] The lid 420 may be positioned in a warming or melting cycle position 450w with the vent 424 fully open. A high flow rate of warmed air may be forced into the conversion chamber 440; the open vent 424 prevents pressure buildup and also allows heat exchange. In this warming or melting cycle position, the cryogenic gas inlet 426 of the lid 420 may be misaligned with the cryogenic gas inlet 470, preventing cryogenic or cold gas from entering the conversion chamber 440, while the warming gas inlet 428 may be aligned with the warming gas inlet 480, allowing warming gas to enter the conversion chamber 440, as in FIG. 4G. The warming air may consist of hot air forced into the conversion chamber 440. The warming air may be, for example, sterile and sourced from a canister. The warming air may consist of, for example, warmed nitrogen gas. In some embodiments, a heating element, such as an induction coil, may be provided near warmed gas inlet 428 and / or warmed gas inlet 480 to independently warm the incoming air. In some embodiments, a UV light emitter may be provided to sterilize the incoming warmed air.

[0057] Referring to FIG. 4L, a method 4000 for processing tissue using a system such as 400 is now described. In step 4010, one or more of the tubes 432 may be loaded with morselized tissue. The morselized tissue may be provided from any tissue morsel device and loaded into one or more of the tubes 432 in morselized form. As described above, as an alternative or in combination with the use of a carousel 430 with tubes 432 for holding the morselized tissue, a mesh assembly as described herein, such as the mesh assembly described further below with reference to FIGS. 6A-6J, may be used. In step 4020, the loaded tubes 432 may be placed in the carousel 430. In step 4030, the carousel 430 may be placed in the conversion chamber 440. In step 4040, a multi-purpose lid 420 may be placed over the carousel 430 in the conversion chamber 440. In step 4050, the carousel 430 and lid 420 may be secured by inserting the lid lock 422. In step 4060, the lid 420 may be positioned in a cryogenic or cooling cycle position 450c. In step 4070, the morselized tissue may be cryogenically treated or cooled in a cryogenic or cooling cycle to kill, destroy, or otherwise inactivate cancerous cells in the morselized tissue. The tissue may be cooled to a threshold temperature, as described further above with respect to method 300. In step 4080, the system 400 may provide an alert that the cryogenic or cooling cycle is complete. In step 4090, the lid 420 may be positioned in a melting or warming cycle 450w. In step 4100, the tissue may be melted and / or warmed in a melting or warming cycle. The tissue may be warmed to a threshold temperature, as described further above with respect to method 300. Although the use of heated air is described, tissue may be heated in other ways as well, such as with heating elements, for example, inductive or resistive heating elements.System 400 may provide an alert that the thawing or warming cycle is complete, and in step 4110, the cooling / warming (i.e., freezing / thawing) may be repeated as commanded by system 400. In some embodiments, repeated cooling and heating may not be necessary. In step 4120, the treated tissue may be removed from tube 432 and tissue treatment system 400. The treated tissue may then be reimplanted, for example, in step 4130. The treated tissue is typically reimplanted in a tissue containment sleeve or bag, but can also be reimplanted alone. One use may be for bone grafting in fusion procedures.

[0058] While the above steps describe a particular method of processing tissue according to many embodiments, those skilled in the art will recognize many variations based on the teachings described herein. Steps may be completed in a different order. Steps may be added or omitted. Some of the steps may include sub-steps. Many of the steps may be repeated as many times as is useful.

[0059] 5A-5K, a tissue processing system 500 and an exemplary method of use 5000 for the system 500 are described. As shown in FIGS. 5A and 5B, the system 500 may include a lid 510 with a lid vent 512, a conversion chamber 520, and a control unit 530, which may include a user interface and / or display. As shown in FIGS. 5C-5F, the conversion chamber 520 may include an oscillating arm 521 coupled to a hanging rod 522 for transporting and moving a tissue tray 523 for holding morselized tissue between a warming pan 524 and a cooling pan 525 (shown in more detail in FIGS. 5H and 5I), such as that indicated by arrow 526 in FIG. 5D. FIG. 5D also shows a liquid level 527 for the warming pan 524 and the cooling pan 525, below which the tissue tray 523 is not placed, to prevent contamination of the held tissue by the warming and cooling liquids. The cooling liquid may be, for example, liquid nitrogen. FIG. 5D shows the tissue tray 523 installed in a cooling pan 525, FIG. 5E shows the tissue tray 523 in a neutral position in the process of being removed from the cooling pan 525, and FIG. 5F shows the tissue tray 523 installed in a warming pan 524. As shown in FIG. 5G, the body of the conversion chamber 520 may comprise a pair of isolated steel pans 523 for the warming and cooling pans 524, 525, as shown in FIG. 5J, for example. The conversion chamber 520 may also include a stepper motor and electronic control 534 and an actuation shaft 536 coupled to the stepper motor and oscillating arm 521 for controlling and moving the oscillating arm 521 according to the current phase of the cooling / warming cycle. As shown in FIGS. 5H and 51, the bottom surface of the tissue tray 523 may be corrugated to provide a large surface area and optimize energy transfer during cooling and warming.

[0060] Referring to FIG. 5K, a method 5000 for processing tissue using a system such as the system 500 is now described. In step 5010, morselized tissue may be placed in a tissue tray 523. The morselized tissue may be provided from any tissue morsel device and loaded into the tissue tray 523 in morselized form. The morselized tissue may be placed in the tray 523 so that all cavities in the scalloped bottom surface are filled and are flush with or less than flush with the surface. In step 5020, a hanging rod 522 may be coupled to the tissue tray 523. In step 5030, the system lid 510 may be opened. In step 5040, the tissue tray 523 may be placed in the conversion chamber 520 by suspending it on the oscillating arm 520, which is typically in a neutral position. In step 5050, a cooling / warming cycle may be initiated by the system 500. The tissue may be cooled and warmed to a threshold temperature, as further described above with respect to method 300. The cooling / freezing of the tissue can kill, destroy, or otherwise inactivate cancerous cells within the morselized tissue. In the cooling / warming cycle, arm 521 may oscillate from the cryogenic / cooling pan to the thawing / warming pan at predetermined intervals to ensure the tissue freezes and thaws. The cycle may occur once or several times. While the use of a warming liquid within the tray is described, the tissue may be warmed in other ways as well, such as with a heating element, e.g., an induction or resistance heating element. In step 5070, the cooling / warming cycle may be terminated by system 500. In step 5080, the treated tissue may be removed from tissue tray 523 and tissue treatment system 500. The treated tissue may then be reimplanted, for example, in step 5090. The treated tissue is typically reimplanted in a tissue containment sleeve or bag, but can also be reimplanted alone. One use may be for bone grafting in fusion procedures.

[0061] While the above steps describe a particular method of processing tissue according to many embodiments, those skilled in the art will recognize many variations based on the teachings described herein. Steps may be completed in a different order. Steps may be added or omitted. Some of the steps may include sub-steps. Many of the steps may be repeated as many times as is useful.

[0062] 6A-6J, a tissue processing system 600 and an exemplary method of use 6000 for the system 600 are described. As shown in FIGS. 6A and 6B, the system 600 may include a system housing 610, a conversion chamber 620, an activation button or control 630, a display or screen 640, flexible tubing 650 for cryogenic gas, a warmed air inlet connector 660, a vent 670, and a cryo-tower lid 680. As shown in FIGS. 6C and 6D, the cryo-tower lid 680 may be opened and a cryo-gas canister 682 may be installed within the cryo-tower of the system 600. The cryo-gas canister 682 may hold a cooling gas, such as nitrogen gas. The system 600 may include a piston 684 coupleable to the cryo-gas canister 682 and operable with a cam 686. As shown in FIG. 6C , in the “on” position, cam 686 may be actuated to advance piston 684 and cryogenic gas canister 682 to an adjustable hard stop 688, opening the cryogenic gas canister's top valve and allowing cryogenic gas to enter conversion chamber 620 via flexible tubing 650. Conversion chamber 620 may removably house a mesh cylinder or mesh assembly 621 for containing morselized tissue. A cryogenic air diffuser 622 may be provided within conversion chamber 620 to diffuse cryogenic air from cryogenic gas canister 682. As shown in FIG. 6D , in the “off” position, cam 686 may be actuated to retract piston 684 and cryogenic gas canister 682, closing the cryogenic gas canister's top valve and preventing cryogenic gas from entering conversion chamber 620 via flexible tubing 650. In this "off" position, heated air may be allowed to enter conversion chamber 620 via heated air inlet (ball) valve 662 and heated air inlet connector 660. The heated air may consist of hot air forced into conversion chamber 620. The heated air may be, for example, sterile and sourced from a canister. The heated air may consist of, for example, heated nitrogen gas.In some embodiments, a heating element, such as an induction coil, may be provided near the heated air inlet valve 662 and / or the heated air inlet connector 660 to independently heat the incoming air. In some embodiments, a UV light emitter may be provided to sterilize the incoming heated air.

[0063] 6E-6I show mesh cylinder or mesh assembly 621 and / or ring (bone) tissue obturator 626 to be used in conjunction with mesh assembly 621. Mesh assembly 621 may include outer mesh layer 623, inner mesh layer 624, and base 627. Ring tissue obturator 626 may be used to position and obturate morselized tissue within the space between outer mesh layer 623 and inner mesh layer 624. A removable funnel 625 and lid 629 may be placed on mesh assembly 621 to guide tissue obturation. After the morselized tissue has been obturated within the space, mesh assembly 621 may be placed within conversion chamber 620. Funnel 629 and lid 625 may be removed prior to placing mesh assembly 621 within conversion chamber 620.

[0064] Referring to FIG. 6J , a method 6000 for processing tissue using a system such as 600 will now be described. In step 6010, a removable funnel 629 and lid 625 may be placed on the inner and outer mesh of the mesh assembly 621. In step 6020, morselized tissue may be placed on the removable funnel 629 and lid 625. The morselized tissue may be provided from any tissue morsel removal device and placed in morselized form on the removable funnel and lid 629. In step 6030, a ring obturator 626 may be used to push the morselized (bone) tissue into the void or space between the inner and outer meshes. In step 6040, the ring obturator 626 and funnel 629 and lid 625 may be removed from the mesh assembly 621. In step 6050, the mesh assembly 621 may be inserted inside the conversion chamber 620. In step 6060, the lid of the conversion chamber 620 may be closed. In step 6070, the conversion chamber 620 with the mesh assembly 621 and tissue may be installed in the console or system housing 610. In step 6080, the cryogenic gas canister 682 may be installed in the console or system housing 610, and the tower lid 680 may be closed. In step 6090, the flexible tubing 650 may be inserted into the conversion chamber lid. In step 6100, a heated air tube may be connected to the heated air inlet connector 660. In step 6110, a cooling / warming cycle may be initiated by the system 600. The tissue may be cooled and warmed to a threshold temperature, as further described above with respect to method 300. The cooling / freezing of the tissue can kill, destroy, or otherwise deactivate cancerous cells within the morselized tissue. The cycle may occur once or several times. Although the use of heated air is described, the tissue may be heated in other ways as well, using a heating element, for example, an inductive or resistive heating element, etc. In step 6120, the cooling / warming cycle may be terminated by system 600.In step 6130, the treated tissue can be removed from mesh assembly 621 and tissue treatment system 600. The treated tissue can then be reimplanted, for example, in step 6140. The treated tissue is typically reimplanted in a tissue containment sleeve or bag, but can also be reimplanted alone. One use could be for bone grafting in a fusion procedure.

[0065] While the above steps describe a particular method of processing tissue according to many embodiments, those skilled in the art will recognize many variations based on the teachings described herein. Steps may be completed in a different order. Steps may be added or omitted. Some of the steps may include sub-steps. Many of the steps may be repeated as many times as is useful.

[0066] While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It is understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention, and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

1. 1. A system for treating cancer, comprising:

1. A tumor tissue processing device comprising: a chamber; a cooling gas inlet; a cold gas canister fluidly connected to the cooling gas inlet; and a warming gas inlet; the chamber is fluidly connected to the cooling gas inlet and the warming gas inlet; the cooling gas inlet is configured to introduce a cooling gas into the chamber; the tumor tissue processing device is configured to process tumor tissue harvested from a subject by inactivating cancer cells within the tumor tissue without destroying tumor antigens in the cancer cells; the tumor tissue processing device is configured to repeat one or more cooling and warming cycles on the tumor tissue; said one or more cooling and warming cycles conforming to a defined range of cooling and warming rates; A system comprising:

2. The system of claim 1 , wherein the tumor tissue collected from the subject comprises one or more of soft tissue or bone tissue.

3. 10. The system of claim 1, further comprising a tissue morcellator configured to morcellate the tumor tissue removed from the subject.

4. The system of claim 3 , wherein the tumor tissue is placed in the chamber and morcellated within the chamber.

5. The system of claim 1 , wherein the tumor tissue processing device inactivates cancer cells in the tumor tissue by destroying the cancer cells.

6. The system of claim 1 , wherein the tumor tissue processing device inactivates the cancer cells by cooling tumor tissue within the tumor tissue.

7. The system of claim 6 , wherein the tumor tissue is cooled after being morselized.

8. The system of claim 6 , wherein the tumor tissue processing device is further configured to warm the cooled tumor tissue.

9. 10. The system of claim 1, wherein the tumor tissue processing device is configured to deactivate the cancer cells upon reaching a threshold number of cooling and warming cycles.

10. The system of claim 6 , wherein the cancer cells are deactivated by reaching a threshold temperature.

11. The system of claim 10 , wherein the cancer cells are deactivated by reaching the threshold temperature for a predetermined period of time.

12. The system of claim 11 , wherein the tumor tissue processing device is configured to cool the tumor tissue to a temperature of −50° C. or lower.

13. 13. The system of claim 12, wherein the tumor tissue processing device is configured to cool the tumor tissue to a temperature of -50°C or below for at least 1 minute.

14. The system of claim 6 , wherein the tumor tissue processing device cools the tumor tissue by treating the tumor tissue with cryogenic temperatures.

15. 15. The system of claim 14, wherein the tumor tissue is cryogenically treated using liquid nitrogen.

16. The system of claim 1 , wherein the chamber comprises a containment sleeve.

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