Autologous vs allogenic cell therapy: key differences and applications

The promises and challenges of autologous vs allogenic cell therapy

The base of a cell therapy are either autologous- or allogeneic-derived cells, which are modified before being reintroduced into a patient.

Advanced therapies like cell-based therapies have emerged as a promising field in regenerative medicine, offering novel treatment approaches for conditions such as cancer, autoimmune diseases, and degenerative disorders. One critical distinction in these therapies is whether the cells come from the patient themselves (autologous) or from a donor (allogeneic). Both approaches have unique benefits and limitations, impacting their clinical application and scalability. This blog article overviews autologous vs allogeneic cell therapy forms, exploring their respective benefits and challenges, with relevant examples from current medical applications.

Autologous Cell Therapy: Definition and Characteristics

Autologous cell therapy employs cells that are collected from the patient, processed, and then reintroduced into the same individual. This strategy is widely used in hematopoietic stem cell transplants, chimeric antigen receptor (CAR)-T cell therapies, and autologous mesenchymal stem cell (MSC) applications.

One of the key advantages of autologous cell therapy is the lack of immune rejection because the transplanted cells are derived from the same patient. Consequently, there is no immunosuppressive therapy needed to support the survival of the graft, which is often essential in allogeneic transplants to prevent graft-versus-host disease (GVHD) (1). Additionally, the reduced risk of adverse immune reactions makes it a safer alternative for patients with compromised immune systems. Nevertheless, autologous therapies also have significant limitations. The preparation process is time-consuming because cells must be harvested, expanded, and sometimes genetically modified before re-administration. This can lead to significant delays in treatment, representing a critical factor in acute conditions such as aggressive cancers (2). Further, the quality and potency of autologous cells are variable and may even be compromised due to factors like the patient's age, underlying disease, or prior treatments. This heterogeneity might affect their therapeutic efficacy (3).

CAR-T Cell Therapy

CAR-T cell therapy is a prominent example of autologous therapy, which is used in the treatment of hematological malignancies. In this approach, T cells from the patients are extracted and genetically engineered to target specific cancer cells. The modified cells are expanded outside the body and re-administered to the patient, where they start an immune attack against the tumor (4). This personalized therapy has demonstrated high remission rates in patients with B-cell lymphomas and leukemias. Despite the promising perspective, the complexity and high cost of manufacturing remain challenges in daily clinical adoption.

Allogenic therapy

In contrast, allogeneic cell therapy relies on the use of cells from an external donor, which can be either matched (HLA-compatible) or universal (off-the-shelf cell lines). A well-known example is hematopoietic stem cell transplantations (HSCT) and mesenchymal stem cell therapy (5).

Importantly, donor-derived allogeneic cell products can be immediately available when needed. They profit from the potential of expanding and cryopreserving until administration. Thus, eliminating the waiting time associated with autologous therapies, making allogeneic treatments particularly suitable for conditions requiring urgent intervention (3). Moreover, allogeneic therapies are easier to scale since cells from a single donor can be expanded and used for multiple patients, reducing manufacturing costs and increasing accessibility. Of these advantages, the main concern using allogeneic therapies is the risk of immune rejection. Patients undergoing allogeneic therapy often require immunosuppressive drugs to prevent such complications, which can increase the risk of infections and other side effects.

Mesenchymal Stem Cell Therapy (MSC)

Recently, an allogeneic MSC product for treating steroid-refractory acute graf-versus-host disease (SR-aGVHD) in pediatric patients was approved by the FDA. The MSCs used in the therapy are derived the bone marrow of healthy adult human donors, expanded in vitro, and administered to patients to induce tissue regeneration and promote immune system modulation with minimal risk of immune rejection due to the immunomodulatory properties of MSCs (6-7).

Major progress in gene editing (e.g., CRISPR) and universal induced pluripotent stem cells (iPSCs) is introducing novel directions for next-generation allogeneic cell therapies that could overcome current limitations. For instance, hypoimmune iPSC-derived cells might avoid immune detection and provide an “off-the-shelf” alternative with low rejection rates (8). In parallel, innovations in bioreactor-based expansion and automation will accelerate the production of autologous therapies, making them more cost-effective.

Autologous and allogeneic cell therapies each have advantages and limitations, influencing their suitability for different medical applications depending on factors such as disease type, urgency, and cost considerations. Autologous therapies provide personalized treatment with minimal immune complications, whereas allogeneic therapies offer faster access and scalability. Ongoing research is focused on optimizing both strategies to enhance safety, efficacy, and accessibility in clinical practice. In the future, the integration of advanced cell engineering, immune modulation, and large-scale cell manufacturing will be crucial to unlock the full potential of cell-based therapies.

Did you know that the CellScrew® system by Green Elephant Biotech offers cell expansion solutions to reduce resources when scaling up your stem cell production? Available in various sizes and 3D-printed from PLA, the CellScrew® allows for seamless scaling of adherent cell cultures, tailored to both research and industrial-scale production needs.

References

1. Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009 May 2;373(9674):1550-61. doi: 10.1016/S0140-6736(09)60237-3. Epub 2009 Mar 11. PMID: 19282026; PMCID: PMC2735047.

2. Holstein SA, Lunning MA. CAR T-Cell Therapy in Hematologic Malignancies: A Voyage in Progress. Clin Pharmacol Ther. 2020 Jan;107(1):112-122. doi: 10.1002/cpt.1674. Epub 2019 Nov 25. PMID: 31622496.

3. Li C, Zhao H, Cheng L et al. Allogeneic vs. autologous mesenchymal stem/stromal cells in their medication practice. Cell Biosci 11, 187 (2021). https://doi.org/10.1186/s13578-021-00698-y

4. Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018 Feb 1;378(5):439-448. doi: 10.1056/NEJMoa1709866. PMID: 29385370; PMCID: PMC5996391.

5. Karantalis V, Schulman IH, Balkan W, Hare JM. Allogeneic cell therapy: a new paradigm in therapeutics. Circ Res. 2015 Jan 2;116(1):12-5. doi: 10.1161/CIRCRESAHA.114.305495. PMID: 25552688; PMCID: PMC4411634.

6. U.S. Food and Drug Administration, FDA Approves First Mesenchymal Stromal Cell Therapy to Treat Steroid-refractory Acute Graft-versus-host Disease, December 18 2024, available from https://www.fda.gov/news-events/press-announcements/fda-approves-first-mesenchymal-stromal-cell-therapy-treat-steroid-refractory-acute-graft-versus-host

7. Jimenez-Puerta GJ, Marchal JA, López-Ruiz E, Gálvez-Martín P. Role of Mesenchymal Stromal Cells as Therapeutic Agents: Potential Mechanisms of Action and Implications in Their Clinical Use. J Clin Med. 2020 Feb 6;9(2):445. doi: 10.3390/jcm9020445. PMID: 32041213; PMCID: PMC7074225.

8. Deuse T, Hu X, Gravina A, Wang D, Tediashvili G, De C, Thayer WO, Wahl A, Garcia JV, Reichenspurner H, Davis MM, Lanier LL, Schrepfer S. Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nat Biotechnol. 2019 Mar;37(3):252-258. doi: 10.1038/s41587-019-0016-3. Epub 2019 Feb 18. Erratum in: Nat Biotechnol. 2022 Nov;40(11):1690. doi: 10.1038/s41587-022-01426-8. PMID: 30778232; PMCID: PMC6419516.