Cellular therapy approaches harnessing the power of the immune system for personalized cancer treatment

Bastien, Jean-Philippe; Minguy, A.; Davé, Vibhuti P.; Roy, Denis

doi:10.1016/j.smim.2019.101306

Cited by 22 publications

(14 citation statements)

References 256 publications

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“…Further, Mo-DC have recently successfully been used to induce viral-specific T cell expansion in virus-naïve donors [36]. This technology could be valuable for a variety of applications such as cancer immunotherapy [2,13], the expansion of tumor or viral reactive T cells, to treat, respectively, cancer or infection-prone immunocompromised patients [37,38] as well as expanding other tolerogenic cells such as regulatory T cells (Tregs) in the context of auto-immunity or graft rejection [39].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…One cell therapy product of major commercial and clinical interest is dendritic cells (DCs) [ 2 ]. Indeed, DCs have been hypothesized to be the panacea for personalized immunotherapy owing to their unique capacity to activate T cells and initiate the adaptive immune response to specifically eliminate target cells that are transformed or infected with pathogens [ 2 – 4 ]. Due to their low frequency of occurrence in peripheral blood, DCs are commonly differentiated ex vivo from monocytes in the presence of cytokines added to culture media, typically interleukin (IL)-4 and macrophage-colony stimulating factor (GM-CSF) [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

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Closing the system: production of viral antigen-presenting dendritic cells eliciting specific CD8+ T cell activation in fluorinated ethylene propylene cell culture bags

et al. 2020

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Background A major obstacle to anti-viral and -tumor cell vaccination and T cell immunotherapy is the ability to produce dendritic cells (DCs) in a suitable clinical setting. It is imperative to develop closed cell culture systems to accelerate the translation of promising DC-based cell therapy products to the clinic. The objective of this study was to investigate whether viral antigen-loaded monocyte-derived DCs (Mo-DCs) capable of eliciting specific T cell activation can be manufactured in fluorinated ethylene propylene (FEP) bags. Methods Mo-DCs were generated through a protocol applying cytokine cocktails combined with lipopolysaccharide or with a CMV viral peptide antigen in conventional tissue culture polystyrene (TCPS) or FEP culture vessels. Research-scale (< 10 mL) FEP bags were implemented to increase R&D throughput. DC surface marker profiles, cytokine production, and ability to activate antigen-specific cytotoxic T cells were characterized. Results Monocyte differentiation into Mo-DCs led to the loss of CD14 expression with concomitant upregulation of CD80, CD83 and CD86. Significantly increased levels of IL-10 and IL-12 were observed after maturation on day 9. Antigen-pulsed Mo-DCs activated antigen-responsive CD8+ cytotoxic T cells. No significant differences in surface marker expression or tetramer-specific T cell activating potency of Mo-DCs were observed between TCPS and FEP culture vessels. Conclusions Our findings demonstrate that viral antigen-loaded Mo-DCs produced in downscaled FEP bags can elicit specific T cell responses. In view of the dire clinical need for closed system DC manufacturing, FEP bags represent an attractive option to accelerate the translation of promising emerging DC-based immunotherapies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Closing the system: production of viral antigen-presenting dendritic cells eliciting specific CD8+ T cell activation in fluorinated ethylene propylene cell culture bags

et al. 2020

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“…Clinical trials have shown that neoantigen-based vaccines do elicit some T cell responses with few severe adverse side effects and when combined with PD-1 checkpoint inhibitors, trial participants receiving both had more durable responses than with either therapy alone [63]. In personalized immune therapy, there is a choice of several types of tumor-associated antigens as well as neoantigens by direct injection that can be used as target antigens to enable T cells to destroy tumor cells [64]. According to these authors, other methods of administration include peptide-loaded DCs in vaccination approaches or infusion of ex vivo expanded tumor-specific T cells, but such cell therapies have potential problems such as immune suppressive tumor microenvironment, lack of persistence of ex vivo expanded antigen-specific T cells, and potential off-target toxicity.…”

Section: Concluding Remarks and The Future Of Personalized Immuno-oncmentioning

confidence: 99%

Personalized Immuno-Oncology

Jain¹

2020

Med Princ Pract

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Cancer immunotherapy, which aims to control the immune system to eradicate cancer cells and prevent their spread, needs to be personalized because anticancer immune responses can be inhibited in several ways that vary from patient to patient. Cancer immunotherapy includes pharmaceuticals such as immune checkpoint inhibitors and monoclonal antibodies (MAbs) as well as cell therapy, immunogene therapy, and vaccines. Combination of programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) drugs with other immunotherapy drugs, for example, antibody-drug conjugates, as well as combination of PD-1/PD-L1 drugs with other therapies, for example, chemotherapy and radiation therapy, are being explored. Biomarkers are important for predicting the response to immunotherapy. Molecular diagnostics and sequencing are important technologies for guiding treatment in immuno-oncology. Genomic profiling of tumor mutational burden may enhance the predictive utility of PD-L1 expression and facilitate personalized combination immunotherapy. Optimization of personalized immuno-oncology requires integration of several technologies and selection of those best suited for an individual patient. Advances in immuno-oncology are also attributed to technologies for targeted delivery of anticancer therapeutics such as antigen-capturing nanoparticles for precision targeting and selective delivery. A breakthrough in cell therapy of cancer is a chimeric antigen receptors-T cell, which combines the antigen-binding site of a MAb with the signal activating machinery of a T cell, freeing antigen recognition from major histocompatibility complex restriction. Gene-editing tools such as clustered regularly interspaced short palindromic repeats have a promising application for removing alloreactivity and decreasing immunogenicity of third-party T cells. In conclusion, personalized immuno-oncology is one of the most promising approaches to management of cancer.

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“…60,61 Moreover, there are also no reports where large scale flexibility analysis was carried out, as it is well known that stable binding of CTL epitopes with membrane receptors can evoke a robust and prolonged immune response in melanoma patients. 62 Overcoming these deficiencies in the present study, the novel epitope for MAGE-A11 was designed by using the high throughput advanced immunoinformatics approaches. The study was highly focussed on the advanced strategy: first, to determine the top-scored CTL epitope from five different algorithms and common consensus epitopes out of them were identified.…”

Section: Epitope Stability Optimization and Population Coverage Analysismentioning

confidence: 99%

Cytotoxic T-lymphocyte elicited therapeutic vaccine candidate targeting cancer against MAGE-A11 carcinogenic protein

et al. 2020

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Immunotherapy is a breakthrough approach for cancer treatment and prevention. By exploiting the fact that cancer cells have overexpression of tumor antigens responsible for its growth and progression, which can be identified and removed by boosting the immune system. In silico techniques have provided efficient ways for developing preventive measures to ward off cancer. Herein, we have designed a potent cytotoxic T-lymphocyte epitope to elicit a desirable immune response against carcinogenic melanoma-associated antigen-A11. Potent epitope was predicted using reliable algorithms and characterized by advanced computational avenue CABS molecular dynamics simulation, for full flexible binding with HLA-A*0201 and androgen receptor to large-scale rearrangements of the complex system. Results showed the potent immunogenic construct (KIIDLVHLL), from top epitopes using five algorithms. Molecular docking analyses showed the strong binding of epitope with HLA-A*0201 and androgen receptor with docking score of -780.6 and -641.06 kcal/mol, respectively. Molecular dynamics simulation analysis revealed strong binding of lead epitope with androgen receptor by involvement of 127 elements through atomic-model study. Full flexibility study showed stable binding of epitope with an average RMSD 2.21 Å and maximum RMSD value of 6.48 Å in optimal cluster density area. The epitope also showed remarkable results with radius of gyration 23.0777 Å, world population coverage of 39.08% by immune epitope database, and TAP affinity IC50 value of 2039.65 nm. Moreover, in silico cloning approach confirmed the expression and translation capacity of the construct within a suitable expression vector. This study paves way for a potential immunogenic construct for prevention of cancer.

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Cellular therapy approaches harnessing the power of the immune system for personalized cancer treatment

Cited by 22 publications

References 256 publications

Closing the system: production of viral antigen-presenting dendritic cells eliciting specific CD8+ T cell activation in fluorinated ethylene propylene cell culture bags

Closing the system: production of viral antigen-presenting dendritic cells eliciting specific CD8+ T cell activation in fluorinated ethylene propylene cell culture bags

Personalized Immuno-Oncology

Cytotoxic T-lymphocyte elicited therapeutic vaccine candidate targeting cancer against MAGE-A11 carcinogenic protein

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