Cyto-Immuno-Therapy for Cancer: A Pathway Elicited by Tumor-Targeted, Cytotoxic Drug-Packaged Bacterially Derived Nanocells

Sagnella, Sharon M.; Yang, Lu; Stubbs, Gemma E.; Boslem, Ebru; Martino-Echarri, Estefanía; Smolarczyk, Katarzyna; Pattison, Stacey L.; Vanegas, Natasha; Clair, Eva St.; Clarke, Stephen; Boockvar, John A.; MacDiarmid, Jennifer; Brahmbhatt, Himanshu

doi:10.1016/j.ccell.2020.02.001

Cited by 44 publications

(40 citation statements)

References 41 publications

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“…The DURAclone technology used here has been successfully applied for the detection of regulatory T cells (Tregs), naïve/memory T cells and other immune cells in the peripheral blood of healthy human donors in previous work (33)(34)(35). Furthermore, the feasibility of this technology for immunomonitoring of cancer patients has been proven by the detection of minimal residual disease (MRD) in myeloma patients and by analyzing blood cells of cancer patients in response to immunotherapeutic nanoparticles (36,37). In addition, the introduced technology is not limited to CD19-targeting CAR approaches and can be readily adapted to the evaluation of other CAR immunotherapies.…”

Section: Discussionmentioning

confidence: 99%

Advanced Flow Cytometry Assays for Immune Monitoring of CAR-T Cell Applications

et al. 2021

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Adoptive immunotherapy using chimeric antigen receptor (CAR)-T cells has achieved successful remissions in refractory B-cell leukemia and B-cell lymphomas. In order to estimate both success and severe side effects of CAR-T cell therapies, longitudinal monitoring of the patient’s immune system including CAR-T cells is desirable to accompany clinical staging. To conduct research on the fate and immunological impact of infused CAR-T cells, we established standardized 13-colour/15-parameter flow cytometry assays that are suitable to characterize immune cell subpopulations in the peripheral blood during CAR-T cell treatment. The respective staining technology is based on pre-formulated dry antibody panels in a uniform format. Additionally, further antibodies of choice can be added to address specific clinical or research questions. We designed panels for the anti-CD19 CAR-T therapy and, as a proof of concept, we assessed a healthy individual and three B-cell lymphoma patients treated with anti-CD19 CAR-T cells. We analyzed the presence of anti-CD19 CAR-T cells as well as residual CD19+ B cells, the activation status of the T-cell compartment, the expression of co-stimulatory signaling molecules and cytotoxic agents such as perforin and granzyme B. In summary, this work introduces standardized and modular flow cytometry assays for CAR-T cell clinical research, which could also be adapted in the future as quality controls during the CAR-T cell manufacturing process.

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Section: Discussionmentioning

confidence: 99%

Advanced Flow Cytometry Assays for Immune Monitoring of CAR-T Cell Applications

et al. 2021

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“…For example, it has been demonstrated that minicells (chassis of mini-SimCells) can be loaded to release super-cytotoxic anti-tumor drug. 51 …”

Section: Discussionmentioning

confidence: 99%

Reprogramming Synthetic Cells for Targeted Cancer Therapy

Lim

Yin

et al. 2022

ACS Synth. Biol.

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Advances in synthetic biology enable the reprogramming of bacteria as smart agents to specifically target tumors and locally release anticancer drugs in a highly controlled manner. However, the bench-to-bedside translation of engineered bacteria is often impeded by genetic instability and the potential risk of uncontrollable replication of engineered bacteria inside the patient. SimCells (simple cells) are chromosome-free bacteria controlled by designed gene circuits, which can bypass the interference of the native gene network in bacteria and eliminate the risk of bacterial uncontrolled growth. Here, we describe the reprogramming of SimCells and mini-SimCells to serve as “safe and live drugs” for targeted cancer therapy. We engineer SimCells to display nanobodies on the surface for the binding of carcinoembryonic antigen (CEA), which is an important biomarker found commonly in colorectal cancer cells. We show that SimCells and mini-SimCells with surface display of anti-CEA nanobody can specifically bind CEA-expressing Caco2 cancer cells in vitro while leaving the non-CEA-expressing SW80 cancer cells untouched. These cancer-targeting SimCells and mini-SimCells induced cancer cell death in vitro by compromising the plasma membrane of cancer cells. The cancer-killing effect can be further enhanced by an aspirin/salicylate inducible gene circuit that converts salicylate into catechol, a potent anticancer. This work highlights the potential of SimCells and mini-SimCells for targeted cancer therapy and lays the foundation for the application of synthetic biology to medicine.

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“…Another way to circumvent tumor resistance is to use highly cytotoxic compoundssuch as the PNU-159682 metabolite [161] that cannot be injected systemically because of their high toxicity. Systemic vectorization of this drug in EGFR-targeted bacterial minicells showed significant tumor reduction and immune activation with no side effects in immunocompetent breast and colorectal murine models but also lung and colorectal human cancer xenografts [162].…”

Section: Fighting Resistancementioning

confidence: 98%

Delivery of cancer therapies by synthetic and bio-inspired nanovectors

et al. 2021

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Background As a complement to the clinical development of new anticancer molecules, innovations in therapeutic vectorization aim at solving issues related to tumor specificity and associated toxicities. Nanomedicine is a rapidly evolving field that offers various solutions to increase clinical efficacy and safety. Main Here are presented the recent advances for different types of nanovectors of chemical and biological nature, to identify the best suited for translational research projects. These nanovectors include different types of chemically engineered nanoparticles that now come in many different flavors of ‘smart’ drug delivery systems. Alternatives with enhanced biocompatibility and a better adaptability to new types of therapeutic molecules are the cell-derived extracellular vesicles and micro-organism-derived oncolytic viruses, virus-like particles and bacterial minicells. In the first part of the review, we describe their main physical, chemical and biological properties and their potential for personalized modifications. The second part focuses on presenting the recent literature on the use of the different families of nanovectors to deliver anticancer molecules for chemotherapy, radiotherapy, nucleic acid-based therapy, modulation of the tumor microenvironment and immunotherapy. Conclusion This review will help the readers to better appreciate the complexity of available nanovectors and to identify the most fitting “type” for efficient and specific delivery of diverse anticancer therapies.

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Cyto-Immuno-Therapy for Cancer: A Pathway Elicited by Tumor-Targeted, Cytotoxic Drug-Packaged Bacterially Derived Nanocells

Cited by 44 publications

References 41 publications

Advanced Flow Cytometry Assays for Immune Monitoring of CAR-T Cell Applications

Advanced Flow Cytometry Assays for Immune Monitoring of CAR-T Cell Applications

Reprogramming Synthetic Cells for Targeted Cancer Therapy

Delivery of cancer therapies by synthetic and bio-inspired nanovectors

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