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EP-4737549-A1 - CELL ENGINEERING MODULE

EP4737549A1EP 4737549 A1EP4737549 A1EP 4737549A1EP-4737549-A1

Abstract

In a one aspect, the present invention relates to a cell engineering module (4) for cell engineering target cells (51) in a mixture (5) comprising the target cells (51) and non-target cells (52), comprising: i) a cell monitoring zone (410) for allowing tracking and classifying individual cells (50) in the mixture (5), wherein classifying a cell (50) comprises determining whether the cell (50) is a target cell (51); and ii) an engineering component (42) in the cell monitoring zone (410) for selectively modifying individual cells (50) at one or more engineering sites (420), wherein the target cells (51) and the non-target cells (52) are randomly distributed in the engineering component (42); wherein the engineering component (42) is adapted for-in operation-being controlled so as to selectively modify only target cells tracked to be at one of the engineering sites (420).

Inventors

  • STAKENBORG, TIM
  • STIRPARO, Rocco
  • PEUMANS, PETER

Assignees

  • Imec VZW

Dates

Publication Date
20260506
Application Date
20241031

Claims (15)

  1. A cell engineering module (4) for cell engineering target cells (51) in a mixture (5) comprising the target cells (51) and non-target cells (52), comprising: i) a cell monitoring zone (410) for allowing tracking and classifying individual cells (50) in the mixture (5), wherein classifying a cell (50) comprises determining whether the cell (50) is a target cell (51); and ii) an engineering component (42) in the cell monitoring zone (410) for selectively modifying individual cells (50) at one or more engineering sites (420), wherein the target cells (51) and the non-target cells (52) are randomly distributed in the engineering component (42); wherein the engineering component (42) is adapted for-in operation-being controlled so as to selectively modify only target cells (51) tracked to be at one of the engineering sites (420).
  2. The cell engineering module (4) according to claim 1, wherein the cell monitoring zone (410) is present within a fluidic channel (6).
  3. The cell engineering module (4) according to any of the previous claims, wherein the cell monitoring zone (410) comprises a cell movement modifying surface (411).
  4. The cell engineering module (4) according to any of the previous claims, wherein the cell monitoring zone (410) comprises at least one transparent surface for imaging cells (50) in the cell monitoring zone (410).
  5. The cell engineering module (4) according to any of the previous claims, wherein the engineering component (42) is adapted for interfacing with a control component (43).
  6. The cell engineering module (4) according to any of the previous claims, wherein the target cells (51) are immune cells, preferably peripheral blood mononuclear cells, more preferably lymphocytes, most preferably T cells or NK cells.
  7. A cartridge (120) comprising the cell engineering module (4) according to any of the previous claims.
  8. A system (1) - comprising (11) a cell engineering module (4) as defined in any of claims 1 to 6, or - adapted for receiving (12) a cartridge (120) as defined in claim 7.
  9. The system (1) according to claim 8, further comprising a control component (43) for controlling the engineering component (42) so as to selectively modify only target cells (51) tracked to be at one of the engineering sites (420).
  10. The system (1) according to claim 8 or 9, further comprising an imaging unit (415), preferably a computational microscopy unit, most preferably a lens-free imaging unit.
  11. The system (1) according to any of claims 8 to 10, further comprising-before the cell engineering module (4)-an apheresis module (3) (3) for separating blood into - a fraction of interest comprising the target cells (51), and - a residual fraction.
  12. The system (1) according to claim 11, wherein the apheresis comprises leukapheresis.
  13. The system (1) according to any of claims 8 to 12, being a vein-to-vein system further comprising: - -before the cell engineering module (4) and, if present, before the apheresis module (3) (3)-an extraction module (2) (2) for drawing blood from a patient; and - -after the cell engineering module (4)-a reinsertion module (5) (5) for transferring the modified target cells (51) back into the patient.
  14. The system (1) according to claim 13, for performing the cell engineering in a closed loop wherein the blood remains within the system (1) from the extraction to the reinsertion.
  15. The system (1) according to any of claims 8 to 14, for cell therapy.

Description

Technical field of the invention The present invention relates to the field of cell engineering, and more specifically to selectively modifying individual target cells within a mixture of target and non-target cells. Background of the invention In the field of cellular biology and medical research, the ability to modify (e.g. genetically) cells at the single-cell level is crucial e.g. for advancements in therapy and for furthering our understanding of cellular functions. Traditional approaches to modifying target cells in a mixture of cells typically involve sorting out the target cells, followed by transduction or transfection of the target cells. These approaches thus typically require the physical separation of target cells from a heterogeneous mixture, which can be inefficient and yield less than optimal results. Moreover, these approaches generally handle cells in batches rather than on an individual basis, limiting control in cell modification tasks. Additionally, sorting is generally done using label-based methods, such fluorescence-activated cell sorting (FACS) or magnetic-activated cell sorting (MACS). These techniques, while effective for certain applications, require the cells to be labelled (e.g. with fluorescent markers for FACS or magnetic beads for MACS). This labelling process not only adds additional steps (e.g. additional sample preparation and wash steps to remove unbound labels or reagents) to the procedure-making it time-consuming, complex and more at risk of cell loss or damage-but also introduces foreign materials that can alter cell behaviour/function and/or cell viability. These issues become exceedingly critical when dealing with rare cell types or when sample sizes are limited. One area in which cell engineering is particularly useful is that of cell therapy. Our immune system plays a pivotal role in defending the body against infections and diseases. It possesses the remarkable ability to adapt and respond to various pathogens and internal threats, including viruses, bacteria, cancerous cells, fibrosis and aging. However, there are instances where the immune system fails to make the right tool to fight back (e.g. for HIV), is too slow and needs to be prepared upfront (e.g. with vaccines), or struggles when the threat is an alteration of our own cells (e.g. in the case of cancer or aging). To bolster the immune system's capacity to fight diseases, various strategies have been developed to prime the immune system for fighting a disease of interest. For example, vaccination is a well-known method that prepares the immune system in advance to combat infections, such as influenza or COVID-19. Another advanced approach involves cell therapies, such as chimeric antigen receptor T (CAR-T) cell therapies, which entail modifying the receptors of T-cells to specifically bind to a particular target antigen on certain cells (e.g. cancer cells). While CAR-T therapies have demonstrated promising results, especially in treating previously untreatable cancers, the production of these therapies is fraught with challenges. The current manufacturing processes for cell therapies are complex and time-consuming, often requiring several weeks to produce a single dose. This involves multiple steps such as cell extraction, selection, modification, and expansion, each necessitating specialized equipment, facilities and personnel. Furthermore, extensive quality control tests at each stage contribute to the overall cost and duration of therapy production. The logistics involved further complicate accessibility, as most manufacturing facilities are centralized, necessitating the transportation of biological materials over long distances, potentially compromising their viability and efficacy. Additionally, cell engineering is also extensively used in lab/research settings; e.g. in gene expression studies, knock-down/out studies, protein production, stem cell research, high-throughput screening, miRNA studies, etc There is thus still a need in the art for ways to modify target cells which address at least some of the issues outlined above. Summary of the invention It is an object of embodiments of the present invention to provide an apparatus for selectively modifying individual target cells in a mixture comprising the target cells and non-target cells. This objective is accomplished by systems, modules, cartridges and methods according to the present invention. The claimed invention is as set out in the appended claims. It is an advantage of embodiments of the present invention that they are capable of selectively modifying target cells, ensuring that only the targeted cells are modified. It is a further advantage of embodiments of the present invention that they allow for the modification of target cells without the necessity of isolating them from a mixture comprising both target and non-target cells. It is yet a further advantage of embodiments of the present invention that they can enable the classificatio