Research Topic

Moving Towards Allogeneic Cellular Therapies: Opportunities and Challenges

About this Research Topic

Adoptive cellular therapy is an attractive approach for the treatment of malignant, infectious, or immune-pathological diseases. In recent years, advancements in cellular manufacturing and bioengineering techniques have enabled the generation of new, potent cellular therapies.

To date, commercially available cell therapies, as well as most products tested in clinical trials, are autologous cell products generated from cells isolated from each patient. Despite the enthusiasm for these new approaches, the widespread use of adoptive cell therapies is still limited by the logistical and financial burden related to the ad hoc generation of personalized cell products. The establishment of allogeneic, universal cellular products for off-the-shelf use is, therefore, an attractive alternative to autologous products. Unfortunately, the use of allogeneic cell therapies across MHC-barriers carries major limitations, namely 1) the risk of induction of Graft-versus-Host-Disease (GvHD) by cellular products containing T cells and 2) the rejection of the administered cells by the host immune system, which might limit their persistence and therefore their efficacy.

Several approaches have been undertaken to limit the risk of GvHD-induction by cellular products, including gene editing to ablate expression of the T cell receptor complex or using alternative cell populations deprived of GvHD-induction potential, including gamma delta T cells, natural killer cells, and invariant natural killer T cells. All of these approaches can reduce the risk of GvHD-induction, thus improving the safety of allogeneic cell products. However, the administration of MHC-mismatched allogeneic cells will invariably result in their rejection by the host immune system. Several strategies have been pursued to prevent this rejection, including gene editing to disrupt MHC-molecules expression and/or optimization of the conditioning regimens administered before infusion.

This Research Topic aims to provide a comprehensive overview of recent advances in the preclinical and clinical development of allogeneic cellular therapies. We welcome the submission of Original Research, Review, Mini-Review, Clinical Trial, and Perspective articles covering the immunological and technical aspects relevant to the development of allogeneic cellular therapies, including, but not limited to:

1. Preclinical and clinical experiences using allogeneic cellular therapies for malignant, infectious, or immune-pathological diseases.
2. Novel cell manufacturing strategies to improve the safety and efficacy of allogeneic cellular therapies.
3. Use of gene-editing strategies to improve the safety and efficacy of allogeneic cellular therapies.
4. Selection of specific cell populations for the generation of allogeneic cell products.
5. Immunomonitoring of allogeneic cellular therapies.
6. Interaction between adoptively transferred cellular products and the host immune system.


Keywords: allogeneic therapies, cell therapy, rejection, off-the-shelf, Graft-versus-Host-Disease


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Adoptive cellular therapy is an attractive approach for the treatment of malignant, infectious, or immune-pathological diseases. In recent years, advancements in cellular manufacturing and bioengineering techniques have enabled the generation of new, potent cellular therapies.

To date, commercially available cell therapies, as well as most products tested in clinical trials, are autologous cell products generated from cells isolated from each patient. Despite the enthusiasm for these new approaches, the widespread use of adoptive cell therapies is still limited by the logistical and financial burden related to the ad hoc generation of personalized cell products. The establishment of allogeneic, universal cellular products for off-the-shelf use is, therefore, an attractive alternative to autologous products. Unfortunately, the use of allogeneic cell therapies across MHC-barriers carries major limitations, namely 1) the risk of induction of Graft-versus-Host-Disease (GvHD) by cellular products containing T cells and 2) the rejection of the administered cells by the host immune system, which might limit their persistence and therefore their efficacy.

Several approaches have been undertaken to limit the risk of GvHD-induction by cellular products, including gene editing to ablate expression of the T cell receptor complex or using alternative cell populations deprived of GvHD-induction potential, including gamma delta T cells, natural killer cells, and invariant natural killer T cells. All of these approaches can reduce the risk of GvHD-induction, thus improving the safety of allogeneic cell products. However, the administration of MHC-mismatched allogeneic cells will invariably result in their rejection by the host immune system. Several strategies have been pursued to prevent this rejection, including gene editing to disrupt MHC-molecules expression and/or optimization of the conditioning regimens administered before infusion.

This Research Topic aims to provide a comprehensive overview of recent advances in the preclinical and clinical development of allogeneic cellular therapies. We welcome the submission of Original Research, Review, Mini-Review, Clinical Trial, and Perspective articles covering the immunological and technical aspects relevant to the development of allogeneic cellular therapies, including, but not limited to:

1. Preclinical and clinical experiences using allogeneic cellular therapies for malignant, infectious, or immune-pathological diseases.
2. Novel cell manufacturing strategies to improve the safety and efficacy of allogeneic cellular therapies.
3. Use of gene-editing strategies to improve the safety and efficacy of allogeneic cellular therapies.
4. Selection of specific cell populations for the generation of allogeneic cell products.
5. Immunomonitoring of allogeneic cellular therapies.
6. Interaction between adoptively transferred cellular products and the host immune system.


Keywords: allogeneic therapies, cell therapy, rejection, off-the-shelf, Graft-versus-Host-Disease


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

15 July 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

15 July 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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