Perspectives on Manufacturing of High-Quality Cell Therapies

Rivière, Isabelle; Roy, Krishnendu

doi:10.1016/j.ymthe.2017.04.010

Cited by 30 publications

(23 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Developing new analytical technologies that will support in-process and the release of a high number of batches (by multiplexing QC tests) will be needed. 259 Biological safety and standards. The provision of a sufficiently high degree of assurance that the environment does not contaminate each batch is of course necessary.…”

Section: Challenges In Delivering Personalised Atmpsmentioning

confidence: 99%

Promises and challenges of adoptive T-cell therapies for solid tumours

et al. 2021

View full text Add to dashboard Cite

Cancer is a leading cause of death worldwide and, despite new targeted therapies and immunotherapies, many patients with advanced-stage- or high-risk cancers still die, owing to metastatic disease. Adoptive T-cell therapy, involving the autologous or allogeneic transplant of tumour-infiltrating lymphocytes or genetically modified T cells expressing novel T-cell receptors or chimeric antigen receptors, has shown promise in the treatment of cancer patients, leading to durable responses and, in some cases, cure. Technological advances in genomics, computational biology, immunology and cell manufacturing have brought the aspiration of individualised therapies for cancer patients closer to reality. This new era of cell-based individualised therapeutics challenges the traditional standards of therapeutic interventions and provides opportunities for a paradigm shift in our approach to cancer therapy. Invited speakers at a 2020 symposium discussed three areas—cancer genomics, cancer immunology and cell-therapy manufacturing—that are essential to the effective translation of T-cell therapies in the treatment of solid malignancies. Key advances have been made in understanding genetic intratumour heterogeneity, and strategies to accurately identify neoantigens, overcome T-cell exhaustion and circumvent tumour immunosuppression after cell-therapy infusion are being developed. Advances are being made in cell-manufacturing approaches that have the potential to establish cell-therapies as credible therapeutic options. T-cell therapies face many challenges but hold great promise for improving clinical outcomes for patients with solid tumours.

show abstract

Section: Challenges In Delivering Personalised Atmpsmentioning

confidence: 99%

Promises and challenges of adoptive T-cell therapies for solid tumours

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Particularly challenging steps to automate such as initial seed or final transfer steps are likely to remain in the realm of the human operator, but recent advances are bringing more of the online monitoring and routine media exchange steps under automation. These future steps are being catalyzed by advances in reactor design, online monitoring technologies (57) and novel separation and purification technologies (58). This progress in automation should present opportunities for reduction on COG alongside increasing homogeneity of manufactured product.…”

Section: Resultsmentioning

confidence: 99%

Ex vivo Manufactured Neutrophils for Treatment of Neutropenia—A Process Economic Evaluation

Torres‐Acosta

Harrison

Csaszar³

et al. 2019

Front. Med.

View full text Add to dashboard Cite

Neutropenia is a common side-effect of acute myeloid leukemia (AML) chemotherapy characterized by a critical drop in neutrophil blood concentration. Neutropenic patients are prone to infections, experience poorer clinical outcomes, and require expensive medical care. Although transfusions of donor neutrophils are a logical solution to neutropenia, this approach has not gained clinical traction, primarily due to challenges associated with obtaining sufficiently large numbers of neutrophils from donors whilst logistically managing their extremely short shelf-life. A protocol has been developed that produces clinical-scale quantities of neutrophils from hematopoietic stem and progenitor cells (HSPC) in 10 L single-use bioreactors ( 1 ). This strategy could be used to mass produce neutrophils and generate sufficient cell numbers to allow decisive clinical trials of neutrophil transfusion. We present a bioprocess model for neutrophil production at relevant clinical-scale. We evaluated two production scenarios, and the impact on cost of goods (COG) of multiple model parameters including cell yield, materials costs, and process duration. The most significant contributors to cost were consumables and raw materials, including the cost of procuring HSPC-containing umbilical cord blood. The model indicates that the most cost-efficient culture volume (batch size) is ~100 L in a single bioreactor. This study serves as a framework for decision-making and optimization strategies when contemplating the production of clinical quantities of cells for allogeneic therapy.

show abstract

“…(75-77) Automated, powerful, and cost-effective cell production platforms compliant with cGMP coupled with robust analytics, ensure reproducible cell quality was now on hunted to commercialize these potent personalized, therapeutic modalities in an efficient, effective manner. (78,79) The fusion proteins genetically engineered in CARs including: (1) an antigen domain, derived from a monoclonal antibody and (2) intracellular T cell signaling and costimulatory domains. (44,62,80-82) The development of CAR-T cell therapy has now expanded beyond phase 1 trials and moved into phase 2 multi-site trials (NCT02435849 and NCT02228096.…”

Section: Cell Sources and Clinical Manufacturing Of Car-t Cellsmentioning

confidence: 99%

CAR T Cells: Precision Cancer Immunotherapy

2018

View full text Add to dashboard Cite

BACKGROUND: Current cancer drugs and treatments are aiming at eradicating tumor cells, but often are more toxic then effective, killing also the normal cells and not selectively the tumor cells. There is good personalized cancer therapy that involves administration to the cancer-bearing host of immune cells with direct anticancer activity, which called adoptive cell therapy (ACT). A review of the unique biology of T cell therapy and of recent clinical experience compels a reassessment of target antigens that traditionally have been viewed from the perspective of weaker immunotherapeutic modalities.CONTENT: Chimeric antigen receptors (CAR) are recombinant receptors which provide both antigen-binding and T cell-activating functions. Many kind of CARs has been reported for the past few years, targeting an array of cell surface tumor antigens. Their biologic functions have extremely changed following the introduction of tripartite receptors comprising a costimulatory domain, termed second-generation CARs. The combination of CARs with costimulatory ligands, chimeric costimulatory receptors, or cytokines can be done to further enhance T cell potency, specificity and safety. CARs reflects a new class of drugs with exciting potential for cancer immunotherapy.SUMMARY: CAR-T cells have been arising as a new modality for cancer immunotherapy because of their potent efficacy against terminal cancers. They are known to exert higher efficacy than monoclonal antibodies and antibodydrug conjugates, and act via mechanisms distinct from T cell receptor-engineered T cells. These cells are constructed by transducing genes encoding fusion proteins of cancer antigen-recognizing single-chain Fv linked to intracellular signaling domains of T cell receptors.KEYWORDS: chimeric antigen receptor, CAR T cells, adoptive cell therapy, ACT, T cell receptor, TCR, cancer, immunotherapy

show abstract

Perspectives on Manufacturing of High-Quality Cell Therapies

Cited by 30 publications

References 16 publications

Promises and challenges of adoptive T-cell therapies for solid tumours

Promises and challenges of adoptive T-cell therapies for solid tumours

Ex vivo Manufactured Neutrophils for Treatment of Neutropenia—A Process Economic Evaluation

CAR T Cells: Precision Cancer Immunotherapy

Contact Info

Product

Resources

About