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Hyper-interleukin-11 novel designer molecular adjuvant targeting gp130 for whole cell cancer vaccines

Authors: Wiktoria Maria, Suchorska; Hanna, Dams-Kozlowska; Urszula, Kazimierczak; Piotr Jan, Wysocki; Andrzej, Mackiewicz;

Hyper-interleukin-11 novel designer molecular adjuvant targeting gp130 for whole cell cancer vaccines

Abstract

Hyper-IL-11 (H11) is a fusion protein comprising IL-11 and soluble IL-11 receptor directly targeting gp130. We evaluated efficacy of H11 as a molecular adjuvant in therapeutic whole tumor cell vaccine formulation.H11 was tested in ectopic and orthotopic murine renal cell carcinoma (RENCA) models. H11 cDNA was transduced into RENCA cells (RENCA-H11). Mice were immunized with RENCA-H11 or control vaccine (RENCA-IRR) in prophylactic, adjuvant and therapeutic settings. Tumor formation, survival and immune mechanisms activated by H11 were studied.Biologically active H11 was secreted by RENCA-H11 cells. Immunization with RENCA-H11 resulted in mounting specific anti-RENCA response. Treatment of tumor bearing mice in adjuvant setting prevented disease recurrence in therapeutic setting eradicated tumors. In induction phase H11 inhibited T-regulatory cell formation and activated recruitment and maturation of dendritic cells. Downstream of immunization tumors were densely infiltrated by CD8(+), CD4(+), NK cells, cells expressing CD8(+)CD69(+) and CD4(+)CD62L(low).H11 is a good candidate for adjuvant of whole tumor cell vaccines. Direct targeting of gp130 leads to induction of specific and long lasting anticancer immune response. Enhancement of tumor antigen presentation, abrogation of immune tolerance, and activation of NK cells and generation of memory cells lead to eradication of existing tumors.

Keywords

Mice, Inbred BALB C, Time Factors, Recombinant Fusion Proteins, Dendritic Cells, CD8-Positive T-Lymphocytes, Interleukin-11, Cancer Vaccines, T-Lymphocytes, Regulatory, Kidney Neoplasms, Killer Cells, Natural, Mice, Adjuvants, Immunologic, Cell Line, Tumor, Cytokine Receptor gp130, Animals, Humans, Female, Interleukin-11 Receptor alpha Subunit, Carcinoma, Renal Cell, Immunologic Memory

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
7
Average
Average
Average
Related to Research communities
Cancer Research