Immunoengineering: Biodegradable Nanoellipsoidal Artificial Antigen Presenting Cells for Antigen Specific T‐Cell Activation (Small 13/2015)

Meyer, Randall A.; Sunshine, Joel C.; Perica, Karlo; Kosmides, Alyssa K.; Aje, Kent; Schneck, Jonathan P.; Green, Jordan J.

doi:10.1002/smll.201570077

Cited by 3 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Section: Morphologymentioning

confidence: 99%

“…One strategy relies on elongating aDCs into an elliptical shape, which has shown higher immunogenicity and superior pharmacokinetic properties in vivo compared to spherical aDCs. [ 47 ] Sunshine et al compared elliptical and spherical aDCs and concluded that increasing the aspect ratio (up to 6.6) led to improved antigen‐specific activation of CD8 + T cells, reduced tumor burden and increased survival. These results seem to be due to increased interaction along the long axis of elliptical aDCs with T cells ( Figure A).…”

Section: Development Of Adcs Inspired By Their Natural Counterpartsmentioning

confidence: 99%

See 1 more Smart Citation

Artificial Dendritic Cells: A New Era of Promising Antitumor Immunotherapy

Mateus

Sebastião

Frasco

et al. 2023

Small

View full text Add to dashboard Cite

The accelerated development of antitumor immunotherapies in recent years has brought immunomodulation into the spotlight. These include immunotherapeutic treatments with dendritic cell (DC)‐based vaccines which can elicit tumor‐specific immune responses and prolong survival. However, this personalized treatment has several drawbacks, including being costly, labor‐intensive, and time consuming. This has sparked interest in producing artificial dendritic cells (aDCs) to open up the possibility of standardized “off‐the‐shelf” protocols and circumvent the cumbersome and expensive personalized medicine. aDCs take advantage of materials that can be designed and tailored for specific clinical applications. Here, an overview of the immunobiology underlying antigen presentation by DCs is provided in an attempt to select the key features to be mimicked and/or improved through the development of aDCs. The inherent properties of aDCs that greatly impact their performance in vivo and, consequently, the fate of the triggered immune response are also outlined.

show abstract

Section: Morphologymentioning

confidence: 99%

Section: Development Of Adcs Inspired By Their Natural Counterpartsmentioning

confidence: 99%

Artificial Dendritic Cells: A New Era of Promising Antitumor Immunotherapy

Mateus

Sebastião

Frasco

et al. 2023

Small

View full text Add to dashboard Cite

show abstract

T cell immunoengineering with advanced biomaterials

Delcassian

Sattler

Dunlop

2017

Integrative Biology

View full text Add to dashboard Cite

show abstract

Functionalized microcarriers improve T cell manufacturing by facilitating migratory memory T cell production and increasing CD4/CD8 ratio

Dwarshuis

Song

Patel

et al. 2019

Preprint

View full text Add to dashboard Cite

7Adoptive cell therapies (ACT) using chimeric antigen receptor (CAR) T cells have shown promise in treating 8 cancer, but manufacturing large numbers of high quality cells remains challenging. Critically, current T cell ex-9 pansion technologies only partially recapitulate the in vivo microenvironment found in the human lymph nodes. 10 In these organs, T cells expand at high cell density with autocrine/paracrine signaling, as well as signals from 11 the extracellular matrix (ECM). Here we describe a T cell expansion system using degradable gelatin microcar-12 riers functionalized with anti-CD3 and anti-CD28 monoclonal antibodies (mAbs), which address several of these 13 shortcomings. We show that using this system, we can achieve approximately 2-fold greater expansion compared 14 to functionalized magnetic beads, the current industry standard. Furthermore, carriers generated higher numbers 15 of CCR7+CD62L+ migratory, central memory T cells and CD4+ T cells across multiple donors. Both these 16 phenotypes have emerged as important for establishing durable and effective responses in patients receiving T 17 cell immunotherapies. We further demonstrate that carriers can achieve greater memory cell yield compared to 18 beads across a range of IL2 concentrations from 20 U/mL to 100 U/mL. These differences were greater at lower 19 IL2 concentrations, indicating that the carriers are more efficient. We optimized this system using a design of 20 experiments (DOE) approach and found that the carrier concentration affects the memory cell yield in a quadratic 21 manner, where high or low concentrations are detrimental to memory formation. Finally, we show that carriers do 22 not hinder CAR transduction and can maintain the CD4 and memory phenotype advantages in CAR-transduced 23 T cells. 24Introduction 25 T cell-based immunotherapies have received great interest from clinicians and industry due to their potential to treat, 26 and often finally cure, cancer and other diseases [1, 2]. In 2017, Novartis and Kite Pharma acquired FDA approval 27 1 for Kymriah and Yescarta respectively, two genetically-modified CAR T cell therapies against B cell malignancies. 28Despite these successes, CAR T cell therapies are constrained by an expensive and difficult-to-scale manufacturing 29 process [3, 4]. 30State-of-the-art manufacturing techniques focus only on anti-CD3 and anti-CD28 activation, typically presented 31 on a microbead (Invitrogen Dynabead, Miltenyi MACS beads) or nanobead (Miltenyi TransACT), but also in soluble 32 forms in the case of antibody tetramers (Expamer) [3,[5][6][7]. These strategies overlook many of the signaling com-33 ponents present in the secondary lymphoid organs where T cells normally expand. Typically, T cells are activated 34 under close cell-cell contact via antigen presenting cells (APCs) such as dendritic cells (DCs), which present peptide-35 major histocompatibility complexs (MHCs) to T cells as well as a variety of other costimulatory signals. These close 36 quarters allow for efficient autocrin...

show abstract

Immunoengineering: Biodegradable Nanoellipsoidal Artificial Antigen Presenting Cells for Antigen Specific T‐Cell Activation (Small 13/2015)

Cited by 3 publications

References 0 publications

Artificial Dendritic Cells: A New Era of Promising Antitumor Immunotherapy

Artificial Dendritic Cells: A New Era of Promising Antitumor Immunotherapy

T cell immunoengineering with advanced biomaterials

Functionalized microcarriers improve T cell manufacturing by facilitating migratory memory T cell production and increasing CD4/CD8 ratio

Contact Info

Product

Resources

About