Ultra-sensitive duplex sequencing for tracking of allogeneic cell therapies

Abstract Clinical need for paradigm shifts in efficacy and safety is driving the rapid and wide-ranging innovation in cell therapies for cancer beyond existing regulatory frameworks. Critical issues emerging during clinical trials frequently reflect unresolved elements of the regulation of innovation conundrum from earlier stages of development. We address this challenge using a global regulators’ perspective on the pre-clinical development of cell therapies, as a navigational aid to intended commercial use which maximises the clinical relevance of developmental data. We examine the implications of tumour targeting based on B cell, NK cell, conventional and unconventional T cell receptor domains; multiplex approaches; genetic manipulation strategies; and autologous versus allogeneic cell sources. We propose that detailed characterisation of both the cell source and final product is critical to optimising manufacture of individualised autologous or off the shelf allogeneic cell therapies, enabling product consistency to underpin extrapolation of clinical trial data to the expected commercial use. We highlight preclinical approaches to characterising target antigens including the Human Cell Atlas initiative, multi-dimensional cell culture, and safety testing against activated, proliferating or stressed control cells. Practical solutions are provided for preclinical toxicity studies when cell therapies target uniquely human tumour antigens, including illustrative mitigation measures for potential toxicity likely to support timely approval of first in human clinical trials. We recommend addressing the regulation of innovation conundrum through serial engagement between innovators and regulators early in the development of cell therapies for cancer, accelerating patient access whilst safeguarding against unacceptable toxicities.

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Process change evaluation framework for allogeneic cell therapies: impact on drug development and commercialization

Regenerative Medicine ◽

10.2217/rme-2015-0034 ◽

2016 ◽

Vol 11 (3) ◽

pp. 287-305 ◽

Cited By ~ 11

Author(s):

Sally Hassan ◽

Hsini Huang ◽

Kim Warren ◽

Behzad Mahdavi ◽

David Smith ◽

...

Keyword(s):

Drug Development ◽

Evaluation Framework ◽

Process Change ◽

Cell Therapies ◽

Allogeneic Cell

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Enhanced Immunomodulation in Inflammatory Environments Favors Human Cardiac Mesenchymal Stromal-Like Cells for Allogeneic Cell Therapies

Frontiers in Immunology ◽

10.3389/fimmu.2019.01716 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 1

Author(s):

Falk Diedrichs ◽

Meaghan Stolk ◽

Karsten Jürchott ◽

Marion Haag ◽

Michael Sittinger ◽

...

Keyword(s):

Cell Therapies ◽

Allogeneic Cell

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A new feeder-free NK cell expansion medium for allogeneic cell therapies

Cytotherapy ◽

10.1016/s146532492100414x ◽

2021 ◽

Vol 23 (5) ◽

pp. S93

Author(s):

E. Heipertz ◽

A. Hungler ◽

E. Gill ◽

M. Vemuri ◽

N. Kaur

Keyword(s):

Cell Expansion ◽

Nk Cell ◽

Cell Therapies ◽

Allogeneic Cell ◽

Expansion Medium

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Emerging Technologies in Scar Management: The Role of Allogeneic Cells

Textbook on Scar Management ◽

10.1007/978-3-030-44766-3_51 ◽

2020 ◽

pp. 451-455

Author(s):

Clarisse Ganier ◽

Sonia Gaucher

Keyword(s):

Cell Therapy ◽

Emerging Technologies ◽

Cell Therapies ◽

Allogeneic Cell ◽

Skin Cell ◽

New Therapeutic Approaches ◽

Allogeneic Cell Therapy ◽

Cell Transplants ◽

Scar Management ◽

Cryo Preservation

AbstractScars caused by burns, chronic ulcers from diabetes, infections, skin cancer surgery, and other genetic or somatic disease could require effective treatment to avoid functional and psychological troubles and even mortality. Most of the current treatments aim to reduce local inflammation but not to prevent scarring. Herein, we discussed about emerging technologies in scar management using allogeneic cell therapy. The industrialised allogeneic cell therapy products and the clinical trials using keratinocytes, fibroblasts or MSCs demonstrated acceleration of skin cell migration and proliferation, control wound scarring, immunomodulatory properties and improved angiogenesis. In addition, allogeneic cell transplants offered the possibility of large pre-fabrication, cryo-preservation, for instantaneous use and repeated applications. Current research exploring allogeneic cell therapies for scar treatment are focusing on grafting of epidermal sheets, cellular dermal substitutes and reconstructed skin equivalent and cell intradermal injections. Advances in knowledge in therapeutic potentials of allogeneic injected cells give rise to new therapeutic approaches such as administration of allogeneic cell-derived extracellular vesicles.

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Challenges and advances in scale-up of label-free downstream processing for allogeneic cell therapies

10.18609/cgti.2017.041 ◽

2017 ◽

Vol 3 (6) ◽

pp. 447-467 ◽

Cited By ~ 4

Author(s):

Fernanda Masri ◽

Marieke A Hoeve ◽

Paul A De Sousa ◽

Nicholas A Willoughby

Keyword(s):

Scale Up ◽

Downstream Processing ◽

Label Free ◽

Cell Therapies ◽

Allogeneic Cell

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Use of an apheresis calculator to promote raw material standardization and donor stewardship for allogeneic cell therapies

Cytotherapy ◽

10.1016/j.jcyt.2020.03.258 ◽

2020 ◽

Vol 22 (5) ◽

pp. S132

Author(s):

J.L. Chain ◽

J. Raley ◽

R. Zamilpa ◽

D. Ward ◽

D. Agee ◽

...

Keyword(s):

Raw Material ◽

Cell Therapies ◽

Allogeneic Cell

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Development of Stem Cell-Derived Immune Cells for Off-the-Shelf Cancer Immunotherapies

Cells ◽

10.3390/cells10123497 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3497

Author(s):

Yan-Ruide Li ◽

Zachary Spencer Dunn ◽

Yang Zhou ◽

Derek Lee ◽

Lili Yang

Keyword(s):

T Cells ◽

Stem Cell ◽

T Cell ◽

Immune Cells ◽

Γδ T Cells ◽

Special Focus ◽

Cell Therapies ◽

Allogeneic Cell ◽

Car T Cell ◽

Car T

Cell-based cancer immunotherapy has revolutionized the treatment of hematological malignancies. Specifically, autologous chimeric antigen receptor-engineered T (CAR-T) cell therapies have received approvals for treating leukemias, lymphomas, and multiple myeloma following unprecedented clinical response rates. A critical barrier to the widespread usage of current CAR-T cell products is their autologous nature, which renders these cellular products patient-selective, costly, and challenging to manufacture. Allogeneic cell products can be scalable and readily administrable but face critical concerns of graft-versus-host disease (GvHD), a life-threatening adverse event in which therapeutic cells attack host tissues, and allorejection, in which host immune cells eliminate therapeutic cells, thereby limiting their antitumor efficacy. In this review, we discuss recent advances in developing stem cell-engineered allogeneic cell therapies that aim to overcome the limitations of current autologous and allogeneic cell therapies, with a special focus on stem cell-engineered conventional αβ T cells, unconventional T (iNKT, MAIT, and γδ T) cells, and natural killer (NK) cells.

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