Allogeneic cell therapies use a single source of cells or tissues to treat one or more patients. In contrast to xenogeneic therapies, where cells or tissues from a different species are used (such as pig cells or tissues in humans), allogeneic cell therapies are derived from a donor of the same species. Donor cells undergo extensive screening and characterization to ensure their safety before being used to establish a master cell bank (MCB). The MCB is the basis for generating allogeneic cell therapies after modification and expansion. Donor tissues are also screened to identify potential pathogens or contaminants that may have been introduced during processing.

Sources of Allogenic Cells

An advantage of allogeneic cell therapy is the multiple potential cell sources, including donated tissues, umbilical cord blood, placenta, bone marrow, and induced pluripotent and embryonic stem cells. Patient-derived samples must be matched to the recipient before transplantation. Matching is assessed by profiling the HLA (human leukocyte antigen)expression patterns found on the cell surface, influencing compatibility and rejection outcomes.

Examples of Allogeneic Cell Therapy

• Mesenchymal stem cell (MSC) therapy: Mesenchymal stem cells exhibit immunomodulatory properties that are advantageous to treat conditions like autoimmune diseases, tissue damage and inflammatory disorders. MSCs have the potential to treat multiple patients from a single donor.
• Hematopoietic stem cell (HSC) transplantation: This involves the transplantation of hematopoietic stem cells from a healthy donor to a recipient with conditions such as leukemia, lymphoma or certain genetic disorders. Due to HLA matching requirements, this strategy is usually person-to-person. However, in some cases, a single donor can be a match for multiple individuals and may choose to donate again if they wish to do so.
• Induced pluripotent stem cell (iPSC) therapy: This involves using iPSCs reprogrammed from adult cells of a donor to generate specific cell types for transplantation into patients with degenerative diseases. Pluripotent stem cell approaches can treat multiple patients.
• Chimeric antigen receptor (CAR) T cell therapy: Allogeneic CAR T cell therapy involves engineering T cells from a donor to express specific receptors that target cancer cells, which are then infused into patients.

Advantages

Allogeneic strategies are particularly suited for “off-the-shelf” supply models, which are essential in urgent medical situations. These therapies utilize donors’ cells, allowing storage and immediate availability to treat multiple patients. This prevents the necessity for personalized cell retrieval and preparation, leading to time and resource savings.

Allogeneic stem cell therapies can also provide superior scalability to autologous treatments, increasing accessibility and potentially lowering manufacturing and patient costs.

Challenges

Allogeneic cell therapies or tissue transplants carry the risk of graft-versus-host disease (GVHD) due to HLA mismatch. GVHD, primarily triggered by donor T cells, can be severe and life-threatening. Physicians and clinicians are constantly exploring ways to reduce the risk of GVHD without impacting treatment efficacy. This may include novel gene editing techniques, targeting specific T cell subsets and disrupting certain biochemical pathways.

The challenge of overcoming the substantial immune system barriers for successful engraftment is a significant hurdle in adopting allogeneic therapies widely. While potent immunosuppressant drugs have enabled organ transplant engraftment, they can lead to severe side effects or rejection. “Mixed chimerism” is an approach being studied to reduce or prevent GVHD by retraining the recipient’s immune system to tolerate donor grafts that may not be a complete match in addition to their immune cells.

Using stem cells in clinical applications has sparked ethical concerns, particularly regarding specific cell sources used in allogeneic therapies. However, utilizing umbilical cord blood as a source of allogeneic stem cells raises minimal ethical concerns due to their designation as medical byproducts.

Promising Applications of Allogeneic Cell Therapy

Hematological Disorders

Allogeneic stem cell transplant (Allo-SCT) holds promise for treating patients diagnosed with cutaneous T cell lymphoma, acute myeloid leukemia, Sezary syndrome and myelodysplastic syndrome. It is considered a critical treatment for individuals with acute lymphocytic leukemia, particularly those who test positive for the Philadelphia chromosome. This is due to the relatively elevated risk of relapse associated with chemotherapy in treating blood cancer. Allo-SCT’s potential to replace dysfunctional cells with healthy HSCs offers a significant therapeutic avenue.

Solid organ transplantation

Advancements in solid organ transplantation have improved the quality of life for patients, yet long-term immunosuppression complications remain a challenge. Balancing immune responses between regulatory and alloreactive systems is vital for graft acceptance. One approach is to modulate regulatory cell populations to promote immune tolerance and reduce the need for extensive immunosuppression.

Regenerative Medicine

Allogeneic adult stem cells are gaining attention for convenient regenerative therapies. They can be engineered to evade the recipient's immune system, offering a solution to resistant barriers in allogeneic treatments. Allogeneic iPSC-derived cardiomyocytes are being explored for severe heart failure and ischemic events.

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