Systemic administration of imiquimod as an adjuvant improves immunogenicity of a tumor-lysate vaccine inducing the rejection of a highly aggressive T-cell lymphoma

Sciullo, Paula Di; Menay, Florencia; Cocozza, Federico; Gravisaco, Marí­a José; Waldner, Claudia; Montagnoli, Claudia

doi:10.1016/j.clim.2019.04.013

Cited by 15 publications

(11 citation statements)

References 46 publications

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“…To date, imidazoquinoline molecules have attracted much attention in cancer immunotherapies. For example, R837 has been tested in different clinical trials such as melanoma (NCT01264731), HPV induced cancer, nonsmall-cell lung cancer (NCT01909752), breast cancer (NCT00821964), and T-cell lymphoma . R848 combined with poly-IC (NCT00948961) or without (NCT00821652) also showed strong adjuvanticity in NY-ESO-1 expressed malignancies .…”

Section: Adjuvants For Enhancing Vaccinationmentioning

confidence: 99%

“…For example, R837 has been tested in different clinical trials such as melanoma 115 (NCT01264731), HPV induced cancer, 116 nonsmall-cell lung cancer 117 (NCT01909752), breast cancer 118 (NCT00821964), and T-cell lymphoma. 119 R848 combined with poly-IC (NCT00948961) or without (NCT00821652) also showed strong adjuvanticity in NY-ESO-1 expressed malignancies. 120 For instance, after recombining NY-ESO-1 epitopes to a human DC targeting monoclonal Ab (mAb), a poly-ICLC-and R848-adjuvanted vaccine (CDX-1401) successfully induced high tumor-specific immunity with good tolerance.…”

Section: Natural Synthetic Molecules Binding Pattern Recognition Rece...mentioning

confidence: 99%

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Chemical Strategies to Boost Cancer Vaccines

2020

Chem. Rev.

120

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Personalized cancer vaccines (PCVs) are reinvigorating vaccine strategies in cancer immunotherapy. In contrast to adoptive T-cell therapy and checkpoint blockade, the PCV strategy modulates the innate and adaptive immune systems with broader activation to redeploy antitumor immunity with individualized tumor-specific antigens (neoantigens). Following a sequential scheme of tumor biopsy, mutation analysis, and epitope prediction, the administration of neoantigens with synthetic long peptide (SLP) or mRNA formulations dramatically improves the population and activity of antigen-specific CD4+ and CD8+ T cells. Despite the promising prospect of PCVs, there is still great potential for optimizing prevaccination procedures and vaccine potency. In particular, the arduous development of tumor-associated antigen (TAA)-based vaccines provides valuable experience and rational principles for augmenting vaccine potency which is expected to advance PCV through the design of adjuvants, delivery systems, and immunosuppressive tumor microenvironment (TME) reversion since current personalized vaccination simply admixes antigens with adjuvants. Considering the broader application of TAA-based vaccine design, these two strategies complement each other and can lead to both personalized and universal therapeutic methods. Chemical strategies provide vast opportunities for (1) exploring novel adjuvants, including synthetic molecules and materials with optimizable activity, (2) constructing efficient and precise delivery systems to avoid systemic diffusion, improve biosafety, target secondary lymphoid organs, and enhance antigen presentation, and (3) combining bioengineering methods to innovate improvements in conventional vaccination, "smartly" re-educate the TME, and modulate antitumor immunity. As chemical strategies have proven versatility, reliability, and universality in the design of T cell-and B cell-based antitumor vaccines, the union of such numerous chemical methods in vaccine construction is expected to provide new vigor and vitality in cancer treatment.

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Section: Adjuvants For Enhancing Vaccinationmentioning

confidence: 99%

Section: Natural Synthetic Molecules Binding Pattern Recognition Rece...mentioning

confidence: 99%

Chemical Strategies to Boost Cancer Vaccines

2020

Chem. Rev.

120

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“…Combined TCR and TLR triggering enhances the activation, proliferation, memory formation and effector function of murine and human CD4 + and CD8 + T cells, 10,13,14,16,19,[24][25][26][27][28][29][30] enhancing the production of the pro-inflammatory cytokines IFN-γ, TNF-α and IL-2. 10,14,16,19,[24][25][26][28][29][30][31][32][33] Furthermore, similar to CD28, 22,23 TLR triggering also lowers the antigen threshold required for TCR triggering. 16,24 Due to their stimulatory capacity to enhance the effector function of both innate and adaptive immune cells, 16,34,35 TLR ligands or the exploitation of TLR signalling could provide novel opportunities for immunotherapy approaches.…”

Section: Introductionmentioning

confidence: 99%

Toll‐like receptor‐2/7‐mediated T cell activation: An innate potential to augment CD8⁺ T cell cytokine production

Heeren¹

2021

Scand J Immunol

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CD8+ T cells are critical to combat pathogens and eradicate malignantly transformed cells. To exert their effector function and kill target cells, T cells produce copious amounts of effector molecules, including the pro‐inflammatory cytokines interferon γ, tumour necrosis factor α and interleukin 2. TCR triggering alone is sufficient to induce cytokine secretion by effector and memory CD8+ T cells. However, T cells can also be directly activated by pathogen‐derived molecules, such as through the triggering of Toll‐like receptors (TLRs). TLR‐mediated pathogen sensing by T cells results in the production of only interferon γ. However, in particular when the antigen load on target cells is low, or when TCR affinity to the antigen is limited, antigen‐experienced T cells can benefit from costimulatory signals. TLR stimulation can also function in a costimulatory fashion to enhance TCR triggering. Combined TCR and TLR triggering enhances the proliferation, memory formation and effector function of T cells, resulting in enhanced production of interferon γ, tumour necrosis factor α and interleukin 2. Therefore, TLR ligands or the exploitation of TLR signalling could provide novel opportunities for immunotherapy approaches. In fact, CD19 CAR T cells bearing an intracellular TLR2 costimulatory domain were recently employed to treat cancer patients in a clinical trial. Here, the current knowledge regarding TLR2/7 stimulation‐induced cytokine production by T cells is reviewed. Specifically, the transcriptional and post‐transcriptional pathways engaged upon TLR2/7 sensing and TLR2/7 signalling are discussed. Finally, the potential uses of TLRs to enhance the anti‐tumor effector function of T cells are explored.

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“…The in vitro anticancer effects of our formulations were examined using a co-culture model comprising cancer-reactive T cells and cancer cells. Total T cells were isolated from the splenocytes of mice that had been immunized with CT26 cancer cell lysates and imiquimod, as previously reported with slight modification [ 12 ]. Briefly, Balb/c mice were injected intraperitoneally with 100 μg CT26 protein lysate mixed with 100 μg imiquimod once per week for 3 weeks.…”

Section: Methodsmentioning

confidence: 99%

DNA-based artificial dendritic cells for in situ cytotoxic T cell stimulation and immunotherapy

Lee

Byun

et al. 2022

Bioactive Materials

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Systemic administration of imiquimod as an adjuvant improves immunogenicity of a tumor-lysate vaccine inducing the rejection of a highly aggressive T-cell lymphoma

Abstract: administration of imiquimod as an adjuvant improves immunogenicity of a tumor-lysate vaccine inducing the rejection of a highly aggressive T-cell lymphoma, Clinical Immunology,

Cited by 15 publications

References 46 publications

Chemical Strategies to Boost Cancer Vaccines

Chemical Strategies to Boost Cancer Vaccines

Toll‐like receptor‐2/7‐mediated T cell activation: An innate potential to augment CD8⁺ T cell cytokine production

DNA-based artificial dendritic cells for in situ cytotoxic T cell stimulation and immunotherapy

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Systemic administration of imiquimod as an adjuvant improves immunogenicity of a tumor-lysate vaccine inducing the rejection of a highly aggressive T-cell lymphoma

Abstract: administration of imiquimod as an adjuvant improves immunogenicity of a tumor-lysate vaccine inducing the rejection of a highly aggressive T-cell lymphoma, Clinical Immunology,

Cited by 15 publications

References 46 publications

Chemical Strategies to Boost Cancer Vaccines

Chemical Strategies to Boost Cancer Vaccines

Toll‐like receptor‐2/7‐mediated T cell activation: An innate potential to augment CD8+ T cell cytokine production

DNA-based artificial dendritic cells for in situ cytotoxic T cell stimulation and immunotherapy

Contact Info

Product

Resources

About

Toll‐like receptor‐2/7‐mediated T cell activation: An innate potential to augment CD8⁺ T cell cytokine production