Biomaterials to enhance antigen-specific T cell expansion for cancer immunotherapy

Isser, Ariel; Livingston, Natalie K.; Schneck, Jonathan P.

doi:10.1016/j.biomaterials.2020.120584

Cited by 51 publications

(28 citation statements)

References 240 publications

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“…The expansion of antigen-specific populations of T cells is a critical but challenging step in adoptive T cell therapy. [27] This holds true for CAR-T cell-based technologies which are increasingly being used to treat hematological malignancies, but whose application to other forms of cancer has not yet met with wide success. In CAR-T cell therapy relatively small numbers of cytotoxic CAR-transduced donor T cells must be expanded ex vivo to obtain numbers adequate to mount an effective in vivo Figure 4.…”

Section: Discussionmentioning

confidence: 99%

Antigen‐Specific Stimulation and Expansion of CAR‐T Cells Using Membrane Vesicles as Target Cell Surrogates

Ukrainskaya

Rubtsov

Pershin

et al. 2021

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Development of CAR‐T therapy led to immediate success in the treatment of B cell leukemia. Manufacturing of therapy‐competent functional CAR‐T cells needs robust protocols for ex vivo/in vitro expansion of modified T‐cells. This step is challenging, especially if non‐viral low‐efficiency delivery protocols are used to generate CAR‐T cells. Modern protocols for CAR‐T cell expansion are imperfect since non‐specific stimulation results in rapid outgrowth of CAR‐negative T cells, and removal of feeder cells from mixed cultures necessitates additional purification steps. To develop a specific and improved protocol for CAR‐T cell expansion, cell‐derived membrane vesicles are taken advantage of, and the simple structural demands of the CAR‐antigen interaction. This novel approach is to make antigenic microcytospheres from common cell lines stably expressing surface‐bound CAR antigens, and then use them for stimulation and expansion of CAR‐T cells. The data presented in this article clearly demonstrate that this protocol produced antigen‐specific vesicles with the capacity to induce stronger stimulation, proliferation, and functional activity of CAR‐T cells than is possible with existing protocols. It is predicted that this new methodology will significantly advance the ability to obtain improved populations of functional CAR‐T cells for therapy.

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Section: Discussionmentioning

confidence: 99%

Antigen‐Specific Stimulation and Expansion of CAR‐T Cells Using Membrane Vesicles as Target Cell Surrogates

Ukrainskaya

Rubtsov

Pershin

et al. 2021

Small

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“…Presumably Nano-sized biomaterials are more readily ingested by antigen-presenting cells (APC) (e.g. Dentric cell (DC) and macrophages (MΦ)) than micro-sized biomaterials or clumped aggregates, and thus more effectively activate/differentiate T cells for robust effector functions and protection [ 36 , 37 ]. In recent years, nanovesicles derived from bacterial protoplast open up a new avenue as an effective, safe delivery system to optimize current chemotherapy and immunization strategies both in cancers and infectious diseases [ 24 , 25 ].…”

Section: Resultsmentioning

confidence: 99%

Nanocages engineered from Bacillus Calmette-Guerin facilitate protective Vγ2Vδ2 T cell immunity against Mycobacterium tuberculosis infection

Zhang

Yang

et al. 2022

J Nanobiotechnol

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Tuberculosis (TB), induced by Mycobacterium tuberculosis (Mtb) infection, remains a top killer among infectious diseases. While Bacillus Calmette-Guerin (BCG) is the sole TB vaccine, the clumped-clustered features of BCG in intradermal immunization appear to limit both the BCG protection efficacy and the BCG vaccination safety. We hypothesize that engineering of clumped-clustered BCG into nanoscale particles would improve safety and also facilitate the antigen-presenting-cell (APC)’s uptake and the following processing/presentation for better anti-TB protective immunity. Here, we engineered BCG protoplasts into nanoscale membraned BCG particles, termed as “BCG-Nanocage” to enhance the anti-TB vaccination efficiency and safety. BCG-Nanocage could readily be ingested/taken by APC macrophages selectively; BCG-Nanocage-ingested macrophages exhibited better viability and developed similar antimicrobial responses with BCG-infected macrophages. BCG-Nanocage, like live BCG bacilli, exhibited the robust capability to activate and expand innate-like T effector cell populations of Vγ2+ T, CD4+ T and CD8+ T cells of rhesus macaques in the ex vivo PBMC culture. BCG-Nanocage immunization of rhesus macaques elicited similar or stronger memory-like immune responses of Vγ2Vδ2 T cells, as well as Vγ2Vδ2 T and CD4+/CD8+ T effectors compared to live BCG vaccination. BCG-Nanocage- immunized macaques developed rapidly-sustained pulmonary responses of Vγ2Vδ2 T cells upon Mtb challenge. Furthermore, BCG- and BCG-Nanocage- immunized macaques, but not saline controls, exhibited undetectable Mtb infection loads or TB lesions in the Mtb-challenged lung lobe and hilar lymph node at endpoint after challenge. Thus, the current study well justifies a large pre-clinical investigation to assess BCG-Nanocage for safe and efficacious anti-TB vaccination, which is expected to further develop novel vaccines or adjuvants. Graphical Abstract

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“…Cancer cells aim to bind them with self-expressed specific receptors so that antitumor signalling and immune attack will be prevented. Then, sufficient tumor-associated antigen-presenting cells (APCs) and tumor infiltrating T cells will be extremely lacking in TME [ 40 , 41 ]. Although the immune defence never gives up, at the end, it is going to be beyond the diagnosing and fighting abilities of natural immune packages thus failing to reverse the immune abnormality [ 42 ].…”

Section: Tumor Immunotherapy and 3d Scaffold Biomaterials: A Brief Su...mentioning

confidence: 99%

Three-dimensional (3D) scaffolds as powerful weapons for tumor immunotherapy

Han

2022

Bioactive Materials

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Biomaterials to enhance antigen-specific T cell expansion for cancer immunotherapy

Cited by 51 publications

References 240 publications

Antigen‐Specific Stimulation and Expansion of CAR‐T Cells Using Membrane Vesicles as Target Cell Surrogates

Antigen‐Specific Stimulation and Expansion of CAR‐T Cells Using Membrane Vesicles as Target Cell Surrogates

Nanocages engineered from Bacillus Calmette-Guerin facilitate protective Vγ2Vδ2 T cell immunity against Mycobacterium tuberculosis infection

Three-dimensional (3D) scaffolds as powerful weapons for tumor immunotherapy

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