Nanobodies: A Game-Changer in Cell-Mediated Immunotherapy for Cancer

Mustafa, Mujahed I.; Mohammed, Ahmed

doi:10.1016/j.slasd.2023.08.008

Cited by 3 publications

(1 citation statement)

References 78 publications

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“…Therefore, compared to conventional CAR-T cells, NbCAR-T cells exhibit a superior anti-tumor function in acidic and hypoxic conditions, such as the tumor microenvironment. Another limitation of traditional CAR T cell therapy is their toxicity, low penetration, and poor persistence in solid tumors (5), whereas the utilization of immune cell-bound nanobodies (ICBNs) has overcome these limitations, resulting in reduced toxicity, improved penetration in solid tumors, and enhanced stability in the tumor microenvironment (15,16).…”

Section: Introductionmentioning

confidence: 99%

Nanobody-based chimeric antigen receptor (NbCAR) T cells for in-vivo cancer immunotherapy: A systematic review

Ebrahimi,

Jabbari,

Mohammadi

et al. 2024

Preprint

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Background: Conventional chimeric antigen receptor (CAR) construct is produced using the ScFv of a target specific antibody and has encountered significant challenges in treating cancer, e.g., adverse effects, T cell exhaustion, safety concerns, and sub optimal efficacy in solid tumors. An alternative approach could be to use the outer portion of a nano antibody, named the VHH, for CAR production. The CAR construct produced with this method is named the "nanobody CAR." Nanobody CAR T cells are less immunogenic, more efficient, and easier to manufacture, and thus might be a reliable alternative approach to overcome the barriers associated with conventional CAR T therapy. Materials and methods: Following a comprehensive search on PubMed, Scopus, Web of Sciences, and Google Scholar, available preclinical animal model studies which focused on the safety and efficacy of nanobody CAR T therapy in cancer were included. Results: 338 studies were identified (up to September 15th, 2023), of which 17 studies used nanobody CAR T cells against tumor cells in animal models of different malignancies, including acute leukemia (seven studies), lymphoma (foure studies), hepatocellular carcinoma (three studies), multiple myeloma (two studies), melanoma (one study), colon adenocarcinoma (one studies), TNBC (one study), lung tumor (one study), ovarian adenocarcinoma (one study), multiple myeloma (two studies), and pancreatic cancer (one study). The most common CAR structure was the second generation and, in some cases, the third generation. CD28, 4 1BB, and ICOS were used as co stimulatory domains in the structure. Compared to the control groups, nanobody CAR T cells had a better performance in reducing tumor volume and improving survival. The included studies incorporated significant heterogeneity regarding their reported outcomes and study design, making it impossible to conduct a meta analysis. The Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool was used to assess the risk of bias, which showed potential bias in the included studies. Conclusion: According to small size, ideal stability, high affinity, and manufacturing practicality, nanobody CAR T cells serve as a promising strategy to improve in vivo mice survival and reduce tumor size. To obtain more reliable results, future studies should focus on diminishing the heterogeneity of study design and bias. Protocol registration: PROSPERO; registration number CRD42023425817, registered June 13th, 2023

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Section: Introductionmentioning

confidence: 99%

Nanobody-based chimeric antigen receptor (NbCAR) T cells for in-vivo cancer immunotherapy: A systematic review

Ebrahimi,

Jabbari,

Mohammadi

et al. 2024

Preprint

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CRISPR/Cas9-mediated knockout strategies for enhancing immunotherapy in breast cancer

2024

Naunyn-Schmiedeberg's Arch Pharmacol

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AKT kinases as therapeutic targets

Hassan,

Menges,

Testa

et al. 2024

J Exp Clin Cancer Res

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AKT, or protein kinase B, is a central node of the PI3K signaling pathway that is pivotal for a range of normal cellular physiologies that also underlie several pathological conditions, including inflammatory and autoimmune diseases, overgrowth syndromes, and neoplastic transformation. These pathologies, notably cancer, arise if either the activity of AKT or its positive or negative upstream or downstream regulators or effectors goes unchecked, superimposed on by its intersection with a slew of other pathways. Targeting the PI3K/AKT pathway is, therefore, a prudent countermeasure. AKT inhibitors have been tested in many clinical trials, primarily in combination with other drugs. While some have recently garnered attention for their favorable profile, concern over resistance and off-target effects have continued to hinder their widespread adoption in the clinic, mandating a discussion on alternative modes of targeting. In this review, we discuss isoform-centric targeting that may be more effective and less toxic than traditional pan-AKT inhibitors and its significance for disease prevention and treatment, including immunotherapy. We also touch on the emerging mutant- or allele-selective covalent allosteric AKT inhibitors (CAAIs), as well as indirect, novel AKT-targeting approaches, and end with a briefing on the ongoing quest for more reliable biomarkers predicting sensitivity and response to AKT inhibitors, and their current state of affairs.

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Nanobodies: A Game-Changer in Cell-Mediated Immunotherapy for Cancer

Cited by 3 publications

References 78 publications

Nanobody-based chimeric antigen receptor (NbCAR) T cells for in-vivo cancer immunotherapy: A systematic review

Nanobody-based chimeric antigen receptor (NbCAR) T cells for in-vivo cancer immunotherapy: A systematic review

CRISPR/Cas9-mediated knockout strategies for enhancing immunotherapy in breast cancer

AKT kinases as therapeutic targets

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