The Toll-Like Receptor 3 Agonist Polyriboinosinic Polyribocytidylic Acid Increases the Numbers of NK Cells with Distinct Phenotype in the Liver of B6 Mice

Salem, Mohamed L.; El‐Naggar, Sabry A.; Mobasher, Maysa A.; Elgharabawy, Rehab M.

doi:10.1155/2020/2489407

Cited by 2 publications

(2 citation statements)

References 52 publications

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“…In addition, our group established poly(I:C) as a potent adjuvant in vaccination regimens (Salem, 2005;Salem, 2006;Salem, 2009;Salem, 2007;Salem et al, 2020). We then conducted the same experiment except this time administering vaccination with or without poly(I:C) on day 7 after adoptive cell transfer and analyzed the cell numbers in the peripheral blood on day 12.…”

Section: Cpg-induced Proliferation Of B Cells Associates With Their A...mentioning

confidence: 99%

“…In this context, we have reported that the TLR3L poly(I:C) is a potent adjuvant for CD8 + T cell responses, through increasing T cell number, function, cytokine production, and anti-tumor response 7,20,21 . These adjuvant effects were associated with increases in the by increasing the numbers of dendritic cells in mice 20,22 and in pancreatic cancer patients as well as increases in the numbers of NK cells in mice 23 . In addition, in vivo administration of poly(I:C) at the peak of dendritic cell (DC) expansion aftercyclophosphamide treatment induces in ammatory cytokine production and increases in the number of activated DCs in lymph nodes 22 .…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Conditioning of Antigen-Reactive CD8 + T Cells with Toll-Like Receptor Agonists Enhances Their Expansion In Vivo in an Adoptive Transfer Mouse Model

Salem¹,

Khalil²,

Sobh³

et al. 2021

SSRN Journal

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Section: Cpg-induced Proliferation Of B Cells Associates With Their A...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In Vitro Conditioning of Antigen-Reactive CD8 + T Cells with Toll-Like Receptor Agonists Enhances Their Expansion In Vivo in an Adoptive Transfer Mouse Model

Salem¹,

Khalil²,

Sobh³

et al. 2021

SSRN Journal

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In vitro conditioning of antigen-reactive CD8+ T cells with toll-like receptor agonists enhances their expansion in vivo in an adoptive transfer mouse model

Salem

Khalil

Sobh

et al. 2022

Preprint

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Background: Anti-cancer adoptive T cell therapy has shown significant anti-tumor responses in cancer patients. This therapy is based on in vitro activation of autologous T cells harvested from a cancer patient and infusing them back through blood. The efficacy of adoptively transferred T cells depends on the in vitro conditioning regimen in particular the type of used cytokines. Aim: This study aimed to use toll like receptors (TLRs) ligands (TLRLs) to condition T cells in vitro as a novel approach instead of cytokines. Methods: Spleen cells were harvested from TCR transgenic C57BL/6 pmel-1 mice, in which CD8+ T cells are engineered to recognize melanoma MHC class-I peptides.Unfractionated splenocytes were cultured for 24 hours in vitro with media or melaoma peptide plus or minus IL-12 (10ng/ml), poly(I:C) (TLR3L; 25ug/ml) or CpG (TLR9L; 10ug/ml). Then, activation, proliferation and cytokine production of the cultured cells were assessed. In another set of experiments, the cultured cells were harvested and infused into syngeneic B6 mice followed by vaccination to evaluate their antigen-specific expansion and contraction. Results: Conditioning of donor splenocytes in vitro with the TLR3L or TLR9L during antigen stimulation increased the antigen specific activation, proliferation, and cytokine production. Interestingly, in vitro treatment of the unfractionated splenocytes with TLR9L enhanced the activation and proliferation of B cells regardless antigen stimulation. Adoptive transfer of TLRL-conditioned peptide stimulated CD8+ T cells into naïve mice showed better survival and higher expansion in response to concomitant vaccination with peptide. Interestingly, in vitro conditioning of CD8+ T cells with TLR9L and in vivo conditioning with TLR3L resulted in the best antigen specific expansion of these cells upon their adoptive transfer into recipient mice. Conclusion: These results show that provision of CD8+ T cells in vitro and in vivo with certain TLR agonists can markedly enhance their antigen specific responses upon their adoptive transfer, opening a potential application of this approach in anti-cancer adoptive immunotherapy.

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The Toll-Like Receptor 3 Agonist Polyriboinosinic Polyribocytidylic Acid Increases the Numbers of NK Cells with Distinct Phenotype in the Liver of B6 Mice

Cited by 2 publications

References 52 publications

<i>In Vitro</i> Conditioning of Antigen-Reactive CD8 <sup>+</sup> T Cells with Toll-Like Receptor Agonists Enhances Their Expansion <i>In Vivo</i> in an Adoptive Transfer Mouse Model

<i>In Vitro</i> Conditioning of Antigen-Reactive CD8 <sup>+</sup> T Cells with Toll-Like Receptor Agonists Enhances Their Expansion <i>In Vivo</i> in an Adoptive Transfer Mouse Model

In vitro conditioning of antigen-reactive CD8+ T cells with toll-like receptor agonists enhances their expansion in vivo in an adoptive transfer mouse model

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