A Novel Approach to Manufacture CAR-T Cells for Clinical Applications

Bajgain, Pradip; Mucharla, Roopa; Anurathapan, Usanarat; Lapteva, Natalia; Leen, Ann M.; Heslop, Helen E.; Rooney, Cliona M.; Vera, Juan F.

doi:10.1016/j.bbmt.2012.11.204

Cited by 4 publications

(5 citation statements)

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“…The G-Rex [27] is a scalable cylindrical static device where the T cells are cultured on a gas-permeable membrane at the base of the device which is partially filled with culture medium. As the cells proliferate samples of medium are taken to measure glucose consumption/lactic acid production.…”

Section: Expansionmentioning

confidence: 99%

GMP CAR-T cell production

Gee

2018

Best Practice & Research Clinical Haematology

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Section: Expansionmentioning

confidence: 99%

GMP CAR-T cell production

Gee

2018

Best Practice & Research Clinical Haematology

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“…These artificial APCs can be modified to express costimulatory molecules (such as CD40, CD80, and CD86) that further help with T cell stimulation. Additionally, artificial APCs can be further engineered to express the antigen targeted by the CAR, leading to selective expansion of CAR + T cells once the artificial receptor gets expressed (shown, e.g., with a PSCA‐specific CAR) . Most often, however, simpler alternatives employing T‐cell activating CD3 and CD28 monoclonal antibodies are used for T cell stimulation; these antibodies coat plasticware or are attached to suspension beads present during T cell culture.…”

Section: Car‐t Cell Manufacturingmentioning

confidence: 99%

Cancer Immunotherapy Using CAR‐T Cells: From the Research Bench to the Assembly Line

Gomes-Silva

Ramos

2017

Biotechnology Journal

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The focus of cancer treatment has recently shifted toward targeted therapies, including immunotherapy, which allow better individualization of care and are hoped to increase the probability of success for patients. Specifically, T cells genetically modified to express chimeric antigen receptors (CARs; CAR-T cells) have generated exciting results. Recent clinical successes with this cutting-edge therapy have helped to push CAR-T cells toward approval for wider use. However, several limitations need to be addressed before the widespread use of CAR-T cells as a standard treatment. Here, a succinct background on adoptive T-cell therapy (ATCT)is given. A brief overview of the structure of CARs, how they are introduced into T cells, and how CAR-T cell expansion and selection is achieved in vitro is then presented. Some of the challenges in CAR design are discussed, as well as the difficulties that arise in large-scale CAR-T cell manufacture that will need to be addressed to achieve successful commercialization of this type of cell therapy. Finally, developments already on the horizon are discussed.

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“…Antigendependent aAPCs are also under investigation. 60 In this technique, peripheral blood mononuclear cells are genetically modified to express both a target tumor-associated antigen and a costimulatory molecule, most notably PSCA antigen, CD80 and 4-1BBL. Stimulation is achieved via co-culture after 10 days, and in one study, this technique was shown to enrich the frequency of CAR T cells from o 40% to nearly 90%.…”

Section: Laboratory Techniques In Development To Increase Manufacturimentioning

confidence: 99%

“…Stimulation is achieved via co-culture after 10 days, and in one study, this technique was shown to enrich the frequency of CAR T cells from o 40% to nearly 90%. 60 When combined with the G-Rex Bioreactor culturing system, this antigen-dependent aAPC approach resulted in nearly 490-fold increase in T cells with only 1 liter of culture medium. 60 Temporary CAR expression The temporary expression of CARs in T cells has been shown in preclinical models via RNA electroporation.…”

Section: Laboratory Techniques In Development To Increase Manufacturimentioning

confidence: 99%

“…60 When combined with the G-Rex Bioreactor culturing system, this antigen-dependent aAPC approach resulted in nearly 490-fold increase in T cells with only 1 liter of culture medium. 60 Temporary CAR expression The temporary expression of CARs in T cells has been shown in preclinical models via RNA electroporation. [61][62][63] One of the benefits of the temporary expression of CARs in T cells is the possibility of examining their clinical safety in a self-limiting manner, particularly if there are concerns regarding the on-target, but off-tumor toxic effects.…”

Section: Laboratory Techniques In Development To Increase Manufacturimentioning

confidence: 99%

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Performance-enhancing drugs: design and production of redirected chimeric antigen receptor (CAR) T cells

2015

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Performance enhancement of the immune system can now be generated through ex vivo gene modification of T cells in order to redirect native specificity to target tumor antigens. This approach combines the specificity of antibody therapy, the expanded response of cellular therapy and the memory activity of vaccine therapy. Recent clinical trials of chimeric antigen receptor (CAR) T cells directed toward CD19 as a stand-alone therapy have shown sustained complete responses in patients with acute lymphoblastic leukemia and chronic lymphocytic leukemia. As these drug products are individually derived from a patient's own cells, a different manufacturing approach is required for this kind of personalized therapy compared with conventional drugs. Key steps in the CAR T-cell manufacturing process include the selection and activation of isolated T cells, transduction of T cells to express CARs, ex vivo expansion of modified T cells and cryopreservation in infusible media. In this review, the steps involved in isolating, genetically modifying and scaling-out the CAR T cells for use in a clinical setting are described in the context of in-process and release testing and regulatory standards.

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A Novel Approach to Manufacture CAR-T Cells for Clinical Applications

Cited by 4 publications

References 0 publications

GMP CAR-T cell production

GMP CAR-T cell production

Cancer Immunotherapy Using CAR‐T Cells: From the Research Bench to the Assembly Line

Performance-enhancing drugs: design and production of redirected chimeric antigen receptor (CAR) T cells

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