A BCMA-specific CAR T cell produced with clinically scalable lentiviral and T cell manufacturing processes has potent anti-multiple myeloma activity

Garrett, Tracy E.; Chekmasova, Alena A.; Evans, John W.; Seidel, Stacie L.; Horton, Holly M.; Latimer, Howard J.; Griecci, Johanna A; Horvath, Christopher; Ryu, Byoung Y.; Friedman, Kevin M.; Morgan, Richard A.

doi:10.1186/2051-1426-3-s2-p124

Cited by 4 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… a Yescarta, US FDA assessment report [ 1 ] b Kymriah, US FDA assessment report [ 2 ] c JCAR017 clinical trial [ 10 , 41 ] d Poirot L. et al [ 22 ] and ASH abstract 887 (2017) [ 23 ] e bb21217 clinical trial [ 19 ], BlueBirdBio/Celgene press release [ 56 ] and Garrett et al [ 57 ] *CALM dose escalation trial, first dose results presented nk = not known Kymriah, Yescarta JCA017 and bb21217 have received the EU PRIME status [ 58 ] …”

Section: Introductionmentioning

confidence: 99%

Chimeric Antigen Receptor T-Cells (CAR T-Cells) for Cancer Immunotherapy – Moving Target for Industry?

Salmikangas¹,

Kinsella²,

Chamberlain³

2018

Pharm Res

View full text Add to dashboard Cite

The first CD19 CAR T-cell products, Kymriah and Yescarta, are entering the US market and also being evaluated for marketing authorization in the EU. This breakthrough has expanded the interest and also investments towards novel chimeric antigen receptor (CAR) designs, both for hematological malignancies and solid tumors. At the same time, there is active development in moving from autologous products to allogeneic, off-the-shelf -products. New manufacturing technologies are also emerging for production of these complex genetically-modified cells and even decentralized manufacturing in hospitals is under consideration. However, the high potency of CAR T-cells is associated with toxicity and not all patients respond to the treatment. In addition, the number of patient and product variables impacting the clinical outcome is high. The race towards novel CAR T treatment options for cancer patients has begun, but without careful design of the constructs and overall understanding of the factors that impact the ultimate outcome in each case, the road towards commercial success may be long and winding. This review discusses the product- and patient-related variables that may pose challenges for the industry and developers both from the scientific and regulatory perspective.

show abstract

Section: Introductionmentioning

confidence: 99%

Chimeric Antigen Receptor T-Cells (CAR T-Cells) for Cancer Immunotherapy – Moving Target for Industry?

Salmikangas¹,

Kinsella²,

Chamberlain³

2018

Pharm Res

View full text Add to dashboard Cite

show abstract

“…The most advanced BCMA-CAR-T cell product for the treatment of r/r MM is idecabtagene vicleucel (lab code ide-cel, bb2121), an investigational BCMA-specific CAR-T cell therapy developed by the US pharma company Brystol Myers Squibb (former company: Celgene ), which is currently under evaluation in the US and Europe to receive marketing authorization [ 70 , 71 ]. Ide-cel consists of autologous T cells transduced with a lentiviral vector to express a BCMA-specific second-generation CAR, which possess 4-1BB as intracellular co-stimulatory domain [ 72 , 73 ]. The MAA is based on the results derived from the pivotal phase 2 KarMMa study evaluating the efficacy and safety of ide-cel in heavily pre-treated patients with relapsed and refractory MM (NCT03361748) [ 71 ].…”

Section: Car-t Cell Therapiesmentioning

confidence: 99%

Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany

2021

View full text Add to dashboard Cite

Chimeric antigen receptor (CAR)-T cell therapies are on the verge of becoming powerful immunotherapeutic tools for combating hematological diseases confronted with pressing medical needs. Lately, CAR-NK cell therapies have also come into focus as novel therapeutic options to address hurdles related to CAR-T cell therapies, such as therapy-induced side effects. Currently, more than 500 CAR-T and 17 CAR-NK cell trials are being conducted worldwide including the four CAR-T cell products Kymriah, Yescarta, Tecartus and Breyanzi, which are already available on the market. Most CAR-T cell-based gene therapy products that are under clinical evaluation consist of autologous enriched T cells, whereas CAR-NK cell-based approaches can be generated from allogeneic donors. Besides modification based on a second-generation CAR, more advanced CAR-immune cell therapeutics are being tested, which utilize precise insertion of genes to circumvent graft-versus-host disease (GvHD) or employ a dual targeting approach and adapter CARs in order to avoid therapy resistance caused by antigen loss. In this review, we are going to take a closer look at the commercial CAR-T cell therapies, as well as on CAR-T and CAR-NK cell products, which are currently under evaluation in clinical trials, that are being conducted in Germany.

show abstract

“…Several companies offer gas permeable bags (GPB) including VueLife (Saint Gobain), Charter Medical and OriGen. GPB are designed to enable a high rate of gas transfer to the cells while maintaining low water permeability enabling culturing of cells in a closed system, unlikely conventional tissue culture flasks, and several groups have demonstrated growth of T cells in these bags ( 39 , 40 ). Although cost effective to implement initially due to low baseline costs and no requirement to purchase specialized equipment, long term costs may be higher due to lack of in-line analytics and automation.…”

Section: Current State and Future Perspectives On Immunotherapy Manufmentioning

confidence: 99%

Industrializing Autologous Adoptive Immunotherapies: Manufacturing Advances and Challenges

Iyer

Bowles

Kim³

et al. 2018

Front. Med.

View full text Add to dashboard Cite

Cell therapy has proven to be a burgeoning field of investigation, evidenced by hundreds of clinical trials being conducted worldwide across a variety of cell types and indications. Many cell therapies have been shown to be efficacious in humans, such as modified T-cells and natural killer (NK) cells. Adoptive immunotherapy has shown the most promise in recent years, with particular emphasis on autologous cell sources. Chimeric Antigen Receptor (CAR)-based T-cell therapy targeting CD19-expressing B-cell leukemias has shown remarkable efficacy and reproducibility in numerous clinical trials. Recent marketing approval of Novartis' Kymriah™ (tisagenlecleucel) and Gilead/Kite's Yescarta™ (axicabtagene ciloleucel) by the FDA further underscores both the promise and legwork to be done if manufacturing processes are to become widely accessible. Further work is needed to standardize, automate, close, and scale production to bring down costs and democratize these and other cell therapies. Given the multiple processing steps involved, commercial-scale manufacturing of these therapies necessitates tighter control over process parameters. This focused review highlights some of the most recent advances used in the manufacturing of therapeutic immune cells, with a focus on T-cells. We summarize key unit operations and pain points around current manufacturing solutions. We also review emerging technologies, approaches and reagents used in cell isolation, activation, transduction, expansion, in-process analytics, harvest, cryopreservation and thaw, and conclude with a forward-look at future directions in the manufacture of adoptive immunotherapies.

show abstract

A BCMA-specific CAR T cell produced with clinically scalable lentiviral and T cell manufacturing processes has potent anti-multiple myeloma activity

Abstract: Garrett et al.: A BCMA-specific CAR T cell produced with clinically scalable lentiviral and T cell manufacturing processes has potent anti-multiple myeloma activity.

Cited by 4 publications

References 0 publications

Chimeric Antigen Receptor T-Cells (CAR T-Cells) for Cancer Immunotherapy – Moving Target for Industry?

Chimeric Antigen Receptor T-Cells (CAR T-Cells) for Cancer Immunotherapy – Moving Target for Industry?

Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany

Industrializing Autologous Adoptive Immunotherapies: Manufacturing Advances and Challenges

Contact Info

Product

Resources

About