Allogeneic Cell Cancer Immunotherapies

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (20 October 2021) | Viewed by 38346

Special Issue Editor


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Guest Editor
Hudson Institute of Medical Research, Monash University and Cartherics Pty. Ltd., Clayton, Australia
Interests: low-cost IVF; pluipotent stem cells; translation of cell therapies; immune stem cell therapies for cancer and infection

Special Issue Information

Dear Colleagues,

Allogeneic immuno-cell therapies are beginning to replace autologous chimeric antigen receptor technologies (CAR-T). The major problem is the recognition of allogeneic cells by the recipient immune system that risks donor cell rejection and graft versus host disease. The approaches that are being developed include the use of compatible CAR-T cells derived from HLA-matched donors, derivation of haplotype-induced pluripotent stem cells (iPSCs), gene knock-out of the T cell receptor (TCR) or the major histocompatibility loci (HLAs), the use of natural killer (NK) cells or NKT cells, or combinations of several of these approaches. Given the success of CAR-T for B cell blood cancers, considerable effort is underway to enable single CAR-T products to treat large numbers of patients in a cost-effective way. The ability of gene stem cells to insert CARs into safe harbor sites in the genome and to knock out checkpoint inhibitor genes that prevent tumor destruction is being trialed in animal models and in early-stage clinical trials. These studies are targeted at multiple blood and solid cancers, and also at cells infected with pathological viruses such as HIV and COVID-19. Early progress is encouraging, but the outcome of human clinical trials remains essential to evaluate the safety and efficacy of these new allogeneic cell therapy approaches.

Prof. Alan Trounson
Guest Editor

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Keywords

  • allogeneic cell therapy
  • CAR-T
  • CAR-NK
  • pluripotent stem cells
  • gene editing
  • cancer
  • infection

Published Papers (6 papers)

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Research

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21 pages, 8048 KiB  
Article
Transfer of Cellular Content from the Allogeneic Cell-Based Cancer Vaccine DCP-001 to Host Dendritic Cells Hinges on Phosphatidylserine and Is Enhanced by CD47 Blockade
by Haoxiao Zuo, Marie-José C. van Lierop, Jorn Kaspers, Remco Bos, Anneke Reurs, Saheli Sarkar, Tania Konry, Alwin Kamermans, Gijs Kooij, Helga E. de Vries, Tanja D. de Gruijl, Alex Karlsson-Parra, Erik H. Manting, Ada M. Kruisbeek and Satwinder Kaur Singh
Cells 2021, 10(11), 3233; https://doi.org/10.3390/cells10113233 - 19 Nov 2021
Cited by 4 | Viewed by 3627
Abstract
DCP-001 is a cell-based cancer vaccine generated by differentiation and maturation of cells from the human DCOne myeloid leukemic cell line. This results in a vaccine comprising a broad array of endogenous tumor antigens combined with a mature dendritic cell (mDC) costimulatory profile, [...] Read more.
DCP-001 is a cell-based cancer vaccine generated by differentiation and maturation of cells from the human DCOne myeloid leukemic cell line. This results in a vaccine comprising a broad array of endogenous tumor antigens combined with a mature dendritic cell (mDC) costimulatory profile, functioning as a local inflammatory adjuvant when injected into an allogeneic recipient. Intradermal DCP-001 vaccination has been shown to be safe and feasible as a post-remission therapy in acute myeloid leukemia. In the current study, the mode of action of DCP-001 was further characterized by static and dynamic analysis of the interaction between labelled DCP-001 and host antigen-presenting cells (APCs). Direct cell–cell interactions and uptake of DCP-001 cellular content by APCs were shown to depend on DCP-001 cell surface expression of calreticulin and phosphatidylserine, while blockade of CD47 enhanced the process. Injection of DCP-001 in an ex vivo human skin model led to its uptake by activated skin-emigrating DCs. These data suggest that, following intradermal DCP-001 vaccination, local and recruited host APCs capture tumor-associated antigens from the vaccine, become activated and migrate to the draining lymph nodes to subsequently (re)activate tumor-reactive T-cells. The improved uptake of DCP-001 by blocking CD47 rationalizes the possible combination of DCP-001 vaccination with CD47 blocking therapies. Full article
(This article belongs to the Special Issue Allogeneic Cell Cancer Immunotherapies)
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16 pages, 3309 KiB  
Article
‘Off-the-Shelf’ Immunotherapy: Manufacture of CD8+ T Cells Derived from Hematopoietic Stem Cells
by Nicholas Boyd, Kellie Cartledge, Huimin Cao, Vera Evtimov, Aleta Pupovac, Alan Trounson and Richard Boyd
Cells 2021, 10(10), 2631; https://doi.org/10.3390/cells10102631 - 2 Oct 2021
Cited by 7 | Viewed by 3515
Abstract
Cellular immunotherapy is revolutionizing cancer treatment. However, autologous transplants are complex, costly, and limited by the number and quality of T cells that can be isolated from and expanded for re-infusion into each patient. This paper demonstrates a stromal support cell-free in vitro [...] Read more.
Cellular immunotherapy is revolutionizing cancer treatment. However, autologous transplants are complex, costly, and limited by the number and quality of T cells that can be isolated from and expanded for re-infusion into each patient. This paper demonstrates a stromal support cell-free in vitro method for the differentiation of T cells from umbilical cord blood hematopoietic stem cells (HSCs). For each single HSC cell input, approximately 5 × 104 T cells were created with an initial five days of HSC expansion and subsequent T cell differentiation over 49 days. When the induced in vitro differentiated T cells were activated by cytokines and anti-CD3/CD28 beads, CD8+ T cell receptor (TCR) γδ+ T cells were preferentially generated and elicited cytotoxic function against ovarian cancer cells in vitro. This process of inducing de novo functional T cells offers a possible strategy to increase T cell yields, simplify manufacturing, and reduce costs with application potential for conversion into chimeric antigen receptor (CAR)-T cells for cancer immunotherapy and for allogeneic transplantation to restore immune competence. Full article
(This article belongs to the Special Issue Allogeneic Cell Cancer Immunotherapies)
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Review

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15 pages, 1768 KiB  
Review
Advances in Allogeneic Cancer Cell Therapy and Future Perspectives on “Off-the-Shelf” T Cell Therapy Using iPSC Technology and Gene Editing
by Yoshiki Furukawa, Yasuharu Hamano, Shuichi Shirane, Shintaro Kinoshita, Yoko Azusawa, Jun Ando, Hiromitsu Nakauchi and Miki Ando
Cells 2022, 11(2), 269; https://doi.org/10.3390/cells11020269 - 13 Jan 2022
Cited by 12 | Viewed by 5032
Abstract
The concept of allogeneic cell therapy was first presented over 60 years ago with hematopoietic stem cell transplantation. However, complications such as graft versus host disease (GVHD) and regimen-related toxicities remained as major obstacles. To maximize the effect of graft versus leukemia, while [...] Read more.
The concept of allogeneic cell therapy was first presented over 60 years ago with hematopoietic stem cell transplantation. However, complications such as graft versus host disease (GVHD) and regimen-related toxicities remained as major obstacles. To maximize the effect of graft versus leukemia, while minimizing the effect of GVHD, donor lymphocyte infusion was utilized. This idea, which was used against viral infections, postulated that adoptive transfer of virus-specific cytotoxic T lymphocytes could reconstitute specific immunity and eliminate virus infected cells and led to the idea of banking third party cytotoxic T cells (CTLs). T cell exhaustion sometimes became a problem and difficulty arose in creating robust CTLs. However, the introduction of induced pluripotent stem cells (iPSCs) lessens such problems, and by using iPSC technology, unlimited numbers of allogeneic rejuvenated CTLs with robust and proliferative cytotoxic activity can be created. Despite this revolutionary concept, several concerns still exist, such as immunorejection by recipient cells and safety issues of gene editing. In this review, we describe approaches to a feasible “off-the-shelf” therapy that can be distributed rapidly worldwide. We also offer perspectives on the future of allogeneic cell cancer immunotherapy. Full article
(This article belongs to the Special Issue Allogeneic Cell Cancer Immunotherapies)
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31 pages, 1781 KiB  
Review
Enhancing a Natural Killer: Modification of NK Cells for Cancer Immunotherapy
by Rasa Islam, Aleta Pupovac, Vera Evtimov, Nicholas Boyd, Runzhe Shu, Richard Boyd and Alan Trounson
Cells 2021, 10(5), 1058; https://doi.org/10.3390/cells10051058 - 29 Apr 2021
Cited by 18 | Viewed by 16245
Abstract
Natural killer (NK) cells are potent innate immune system effector lymphocytes armed with multiple mechanisms for killing cancer cells. Given the dynamic roles of NK cells in tumor surveillance, they are fast becoming a next-generation tool for adoptive immunotherapy. Many strategies are being [...] Read more.
Natural killer (NK) cells are potent innate immune system effector lymphocytes armed with multiple mechanisms for killing cancer cells. Given the dynamic roles of NK cells in tumor surveillance, they are fast becoming a next-generation tool for adoptive immunotherapy. Many strategies are being employed to increase their number and improve their ability to overcome cancer resistance and the immunosuppressive tumor microenvironment. These include the use of cytokines and synthetic compounds to bolster propagation and killing capacity, targeting immune-function checkpoints, addition of chimeric antigen receptors (CARs) to provide cancer specificity and genetic ablation of inhibitory molecules. The next generation of NK cell products will ideally be readily available as an “off-the-shelf” product and stem cell derived to enable potentially unlimited supply. However, several considerations regarding NK cell source, genetic modification and scale up first need addressing. Understanding NK cell biology and interaction within specific tumor contexts will help identify necessary NK cell modifications and relevant choice of NK cell source. Further enhancement of manufacturing processes will allow for off-the-shelf NK cell immunotherapies to become key components of multifaceted therapeutic strategies for cancer. Full article
(This article belongs to the Special Issue Allogeneic Cell Cancer Immunotherapies)
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26 pages, 1588 KiB  
Review
Immune Checkpoints in Pediatric Solid Tumors: Targetable Pathways for Advanced Therapeutic Purposes
by Claudia Cocco, Fabio Morandi and Irma Airoldi
Cells 2021, 10(4), 927; https://doi.org/10.3390/cells10040927 - 17 Apr 2021
Cited by 7 | Viewed by 3170
Abstract
The tumor microenvironment (TME) represents a complex network between tumor cells and a variety of components including immune, stromal and vascular endothelial cells as well as the extracellular matrix. A wide panel of signals and interactions here take place, resulting in a bi-directional [...] Read more.
The tumor microenvironment (TME) represents a complex network between tumor cells and a variety of components including immune, stromal and vascular endothelial cells as well as the extracellular matrix. A wide panel of signals and interactions here take place, resulting in a bi-directional modulation of cellular functions. Many stimuli, on one hand, induce tumor growth and the spread of metastatic cells and, on the other hand, contribute to the establishment of an immunosuppressive environment. The latter feature is achieved by soothing immune effector cells, mainly cytotoxic T lymphocytes and B and NK cells, and/or through expansion of regulatory cell populations, including regulatory T and B cells, tumor-associated macrophages and myeloid-derived suppressor cells. In this context, immune checkpoints (IC) are key players in the control of T cell activation and anti-cancer activities, leading to the inhibition of tumor cell lysis and of pro-inflammatory cytokine production. Thus, these pathways represent promising targets for the development of effective and innovative therapies both in adults and children. Here, we address the role of different cell populations homing the TME and of well-known and recently characterized IC in the context of pediatric solid tumors. We also discuss preclinical and clinical data available using IC inhibitors alone, in combination with each other or administered with standard therapies. Full article
(This article belongs to the Special Issue Allogeneic Cell Cancer Immunotherapies)
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Other

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12 pages, 1517 KiB  
Perspective
Induced CAR-Macrophages as a Novel Therapeutic Cell Type for Cancer Immune Cell Therapies
by Siyu Su, Anhua Lei, Xudong Wang, Hengxing Lu, Shuhang Wang, Yuqi Yang, Ning Li, Yi Zhang and Jin Zhang
Cells 2022, 11(10), 1652; https://doi.org/10.3390/cells11101652 - 16 May 2022
Cited by 20 | Viewed by 5496
Abstract
The Chimeric antigen receptor (CAR)-T cell therapy has made inroads in treating hematological malignancies. Nonetheless, there are still multiple hurdles in CAR-T cell therapy for solid tumors. Primary CAR-expressing macrophage cells (CAR-Ms) and induced pluripotent stem cells (iPSCs)-derived CAR-expressing macrophage cells (CAR-iMacs) have [...] Read more.
The Chimeric antigen receptor (CAR)-T cell therapy has made inroads in treating hematological malignancies. Nonetheless, there are still multiple hurdles in CAR-T cell therapy for solid tumors. Primary CAR-expressing macrophage cells (CAR-Ms) and induced pluripotent stem cells (iPSCs)-derived CAR-expressing macrophage cells (CAR-iMacs) have emerged as attractive alternatives in our quest for an efficient and inexpensive approach for tumor immune cell therapy. In this review, we list the current state of development of human CAR-macrophages and provide an overview of the crucial functions of human CAR-macrophages in the field of tumor immune cell therapy. Full article
(This article belongs to the Special Issue Allogeneic Cell Cancer Immunotherapies)
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