Synthetic TRP2 long-peptide and α-galactosylceramide formulated into cationic liposomes elicit CD8 + T-cell responses and prevent tumour progression

Neumann, Silke; Young, Katie; Compton, Benjamin J.; Anderson, Regan J.; Painter, Gavin F.; Hook, Sarah

doi:10.1016/j.vaccine.2015.08.083

Cited by 33 publications

(31 citation statements)

References 43 publications

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“…We have recently shown that a therapeutic vaccine, consisting of a long TRP2-peptide co-delivered with α-GalCer in cationic liposomes, increased cytotoxic T-cell responses, and improved tumor survival in melanoma-bearing mice (24). To investigate if the antitumor efficacy of the vaccine could be enhanced, the dual COX-2/5-LO inhibitor licofelone was added to the therapy.…”

Section: Resultsmentioning

confidence: 99%

“…Cationic liposomes containing the long TRP2-peptide and αGalCer were prepared by hydrating thin lipid films as described previously (24). For some formulations, 4.43 mg licofelone was added to the lipid precursor prior to hydration.…”

Section: Methodsmentioning

confidence: 99%

“…BM was extracted from the hind limbs as described previously (24). The cells were re-suspended at 1 × 10 6 cells/mL and incubated with the following antibodies after non-specific binding was blocked by incubation with Fc receptor block (F16/32): CD11b PE-Cy7, Gr-1 FITC, CD11c APC, F4/80 brilliant violet 421, and CD3 APC-Cy7 (all antibodies were purchased from Biolegend, New Zealand and were titrated on splenocytes and BM cells).…”

Section: Methodsmentioning

confidence: 99%

“…To prepare target T-cells, spleens were dissected from naive OT-I mice and CD43 + cells were isolated by positive selection on an AutoMACS Pro Separator (Miltenyi Biotec) to exclude B-cells. CFSE labeled (24) CD43 + splenocytes were seeded at 5 × 10 4 cells/well in a 96 well round-bottom plate and stimulated with the CD8 epitope of ovalbumin (SIINFEKL; 0.01 μg/mL) in the presence or absence of IMCs for 48 h. IMCs were generated in vitro as described above and incubated with licofelone (5 μM) for 20 h before LPS (50 ng/mL) was added for 4 h. Cells were washed, re-suspended, and added to the sorted splenocytes at the indicated ratios. After 48 h the proliferation of T-cells was assessed by flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

“…To test this hypothesis, licofelone was administered to mice following implantation of tumor cells and was incorporated into a therapeutic liposomal cancer vaccine containing a long peptide and the adjuvant α-galactosylceramide (α-GalCer), previously shown to increase tumor survival in a melanoma model (24). Immunization with long peptides containing both a CD4 and CD8 T-cell epitope induce improved immune responses as compared to minimal T-cell epitopes, which do not require processing prior to presentation on MHC molecules and can induce tolerance (25, 26).…”

Section: Introductionmentioning

confidence: 99%

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Improved Antitumor Activity of a Therapeutic Melanoma Vaccine through the Use of the Dual COX-2/5-LO Inhibitor Licofelone

et al. 2016

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Immune-suppressive cell populations impair antitumor immunity and can contribute to the failure of immune therapeutic approaches. We hypothesized that the non-steroidal anti-inflammatory drug licofelone, a dual cyclooxygenase-2/5-LO inhibitor, would improve therapeutic melanoma vaccination by reducing immune-suppressive cell populations. Therefore, licofelone was administered after tumor implantation, either alone or in combination with a peptide vaccine containing a long tyrosinase-related protein 2-peptide and the adjuvant α-galactosylceramide, all formulated into cationic liposomes. Mice immunized with the long-peptide vaccine and licofelone showed delayed tumor growth compared to mice given the vaccine alone. This protection was associated with a lower frequency of immature myeloid cells (IMCs) in the bone marrow (BM) and spleen of tumor-inoculated mice. When investigating the effect of licofelone on IMCs in vitro, we found that the prostaglandin E2-induced generation of IMCs was decreased in the presence of licofelone. Furthermore, pre-incubation of BM cells differentiated under IMC-inducing conditions with licofelone reduced the secretion of cytokines interleukin (IL)-10 and -6 upon lipopolysaccharides (LPS) stimulation as compared to untreated cells. Interestingly, licofelone increased IL-6 and IL-10 secretion when administered after the LPS stimulus, demonstrating an environment-dependent effect of licofelone. Our findings support the use of licofelone to reduce tumor-promoting cell populations.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Improved Antitumor Activity of a Therapeutic Melanoma Vaccine through the Use of the Dual COX-2/5-LO Inhibitor Licofelone

et al. 2016

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Small‐Molecule Carbohydrate‐Based Immunostimulants

Marzabadi

Franck

2016

Chemistry A European J

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In this review, we discuss small-molecule, carbohydrate-based immunostimulants that target Toll-like receptor 4 (TLR-4) and cluster of differentiation 1D (CD1d) receptors. The design and use of these molecules in immunotherapy as well as results from their use in clinical trials are described. How these molecules work and their utilization as vaccine adjuvants are also discussed. Future applications and extensions for the use of these analogues as therapeutic agents will be outlined.

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Immunostimulation and Immunosuppression: Nanotechnology on the Brink

et al. 2018

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Immunotherapy is revolutionizing current therapies in cancer and in autoimmune diseases, showing impressive results in clinical trials. Recently, the development of innovative nano‐biomaterials has been focusing on the interactions between such materials and the immune system, both in the adaptive and innate branches. Biomaterials can display immunostimulative, neutral, or immunosuppressive interactions. Nanoparticles displaying immunostimulative potential are employed in the formulation of cancer vaccines, while immunosuppressive materials are being researched for the development of vaccines able to induce tolerance in autoimmune diseases. Here, the properties influencing the immunomodulation effect of nanomaterials are analyzed, followed by a detailed review of the recent applications of nanomaterials for the delivery of antigens, adjuvants, chemotherapeutics, and immunomodulatory drugs.

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Synthetic TRP2 long-peptide and α-galactosylceramide formulated into cationic liposomes elicit CD8 + T-cell responses and prevent tumour progression

Cited by 33 publications

References 43 publications

Improved Antitumor Activity of a Therapeutic Melanoma Vaccine through the Use of the Dual COX-2/5-LO Inhibitor Licofelone

Improved Antitumor Activity of a Therapeutic Melanoma Vaccine through the Use of the Dual COX-2/5-LO Inhibitor Licofelone

Small‐Molecule Carbohydrate‐Based Immunostimulants

Immunostimulation and Immunosuppression: Nanotechnology on the Brink

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