Late Boosting of the RV144 Regimen Improves the Magnitude and Quality of Immune Responses

2019 ◽  
Author(s):  
Punnee Pitisuttithum ◽  
Sorachai Nitayapha ◽  
Suwat Chariyalertsak ◽  
Jaranit Kaewkungwal ◽  
Peter Dawson ◽  
...  
Keyword(s):  
Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1448 ◽  
Author(s):  
Stella Logotheti ◽  
Brigitte M. Pützer

Melanoma is a skin cancer which can become metastatic, drug-refractory, and lethal if managed late or inappropriately. An increasing number of melanoma patients exhibits autoimmune diseases, either as pre-existing conditions or as sequelae of immune-based anti-melanoma therapies, which complicate patient management and raise the need for more personalized treatments. STAT3 and/or STAT5 cascades are commonly activated during melanoma progression and mediate the metastatic effects of key oncogenic factors. Deactivation of these cascades enhances antitumor-immune responses, is efficient against metastatic melanoma in the preclinical setting and emerges as a promising targeting strategy, especially for patients resistant to immunotherapies. In the light of the recent realization that cancer and autoimmune diseases share common mechanisms of immune dysregulation, we suggest that the systemic delivery of STAT3 or STAT5 inhibitors could simultaneously target both, melanoma and associated autoimmune diseases, thereby decreasing the overall disease burden and improving quality of life of this patient subpopulation. Herein, we review the recent advances of STAT3 and STAT5 targeting in melanoma, explore which autoimmune diseases are causatively linked to STAT3 and/or STAT5 signaling, and propose that these patients may particularly benefit from treatment with STAT3/STAT5 inhibitors.


2004 ◽  
Vol 11 (6) ◽  
pp. 1100-1104 ◽  
Author(s):  
Jo Southern ◽  
Sarah Deane ◽  
Lindsey Ashton ◽  
Ray Borrow ◽  
David Goldblatt ◽  
...  

ABSTRACT Extensive use of meningococcal AC polysaccharide (MACP) vaccines has raised concerns about induction of immunologic hyporesponsiveness to C polysaccharide. We investigated the immunogenicity and safety of a meningococcal C-tetanus conjugate (MCC-TT) vaccine in naïve adults and prior MACP vaccinees. Laboratory staff (n = 113) were recruited; 73 were naïve to meningococcal vaccination, and 40 had previously received ≥1 dose of MACP vaccine. Blood was taken prior to MCC-TT vaccination and 1 week, 1 month, and 6 months later. At each time point, proportions of subjects with serum bactericidal antibody (SBA) titers of ≥8 or ≥128 were similar (P > 0.46); >94% of subjects achieved titers of ≥128 at 1 month. However, the geometric mean titer (GMT) of SBA at 1 month was higher in the naïve (1,757; 95% confidence interval [95% CI], 1,102 to 2,803) than in the previously vaccinated (662; 95% CI, 363 to 1,207) group (P = 0.02), and similarly at 6 months (P < 0.001). Conversely, geometric mean concentrations (GMCs) of serogroup C-specific immunoglobulin G (IgG) were significantly higher in the previously vaccinated group pre-MCC-TT and at 1 week; the groups were similar at 1 month, and there was some evidence that the GMC for the previously vaccinated group was higher at 6 months. Qualitative differences in antibodies between groups were demonstrated by using the SBA/IgG ratio, though avidity measures were similar for the two groups throughout the study. MCC-TT was well tolerated, with similar safety profiles in the two groups. Pain in the arm and headache were the most frequently reported events following vaccination. The study shows that MCC-TT is safe and immunogenic in naïve and previously MACP-vaccinated adults, though the magnitude and persistence of postvaccination SBA responses in the latter group were lower.


Vaccine ◽  
2012 ◽  
Vol 30 (52) ◽  
pp. 7541-7546 ◽  
Author(s):  
Armando Stano ◽  
Chiara Nembrini ◽  
Melody A. Swartz ◽  
Jeffrey A. Hubbell ◽  
Eleonora Simeoni

2015 ◽  
Vol 2015 ◽  
pp. 1-20 ◽  
Author(s):  
Giulia Gigliobianco ◽  
Sabiniano Roman Regueros ◽  
Nadir I. Osman ◽  
Julio Bissoli ◽  
Anthony J. Bullock ◽  
...  

Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) are major health issues that detrimentally impact the quality of life of millions of women worldwide. Surgical repair is an effective and durable treatment for both conditions. Over the past two decades there has been a trend to enforce or reinforce repairs with synthetic and biological materials. The determinants of surgical outcome are many, encompassing the physical and mechanical properties of the material used, and individual immune responses, as well surgical and constitutional factors. Of the current biomaterials in use none represents an ideal. Biomaterials that induce limited inflammatory response followed by constructive remodelling appear to have more long term success than biomaterials that induce chronic inflammation, fibrosis and encapsulation. In this review we draw upon published animal and human studies to characterize the changes biomaterials undergo after implantation and the typical host responses, placing these in the context of clinical outcomes.


1998 ◽  
Vol 66 (11) ◽  
pp. 5329-5336 ◽  
Author(s):  
George S. N. Hui ◽  
Caryn N. Hashimoto

Vaccine adjuvants exert critical and unique influences on the quality of immune responses induced during active immunizations. We investigated the mechanisms of action of immunological adjuvants in terms of their requirements for cytokine-mediated pathways for adjuvanticity. Antibody responses potentiated by several adjuvants to a Plasmodium falciparum MSP1-19 (C-terminal 19-kDa processing fragment of MSP1) vaccine were studied in gamma interferon (IFN-γ) or interleukin (IL-4) knockout mice. The levels of anti-MSP1-19 antibodies and the induction of Th1- and Th2-type antibodies were analyzed. Results revealed a spectrum of requirements for cytokine-mediated pathways in the potentiation of immunogenicity, and such requirements were influenced by interactions among individual components of the adjuvant formulations. One adjuvant strictly depended on IFN-γ to induce appreciable levels of anti-MSP1-19 antibodies, while some formulations required IFN-γ only for the induction of Th1-type antibodies. Other formulations induced exclusively Th2-type antibodies and were not affected by IFN-γ knockout. There were three patterns of requirements for IL-4 by various adjuvants in the induction of Th2-type anti-MSP1-19 antibodies. Moreover, the induction of Th1-type anti-MSP1-19 antibodies by adjuvants showed two distinct patterns of regulation by IL-4. The utilization of an IL-4 regulated pathway(s) for the induction of Th2-type antibodies by the same adjuvant differed between mouse strains, suggesting that animal species variability in responses to vaccine adjuvants may be due, at least in part, to differences in the utilization of immune system pathways by an adjuvant among animal hosts.


2014 ◽  
Vol 30 (S1) ◽  
pp. A195-A195
Author(s):  
Thomas Vazquez ◽  
Léa Torrieri-Dramard ◽  
Fabien Pitoiset ◽  
James Vigneron ◽  
David Klatzmann ◽  
...  

EP Europace ◽  
2003 ◽  
Vol 4 (Supplement_2) ◽  
pp. B177-B177
Author(s):  
G. Theodorakis ◽  
P. Flevari ◽  
F. Kolokathis ◽  
E. Livanis ◽  
S. Adamopoulos ◽  
...  

2011 ◽  
Vol 1 (1) ◽  
pp. 14
Author(s):  
Michael Vallop Josiassen ◽  
Kajsa Paulsson

Clinical trials and experimental models indicate that dendritic-cell-based immunotherapy is promising for treatment of different types of cancer. However, dendritic cells (DCs) have strong immune-regulatory capacities and can not only stimulate but also dampen immune responses. It is also well known that the different DC subsets strongly influence the magnitude and quality of adaptive immune responses. In this review, to improve understanding of the DC-based immunotherapy approach, we briefly describe different DC subsets and the differentiation, maturation, and activation of these cells. One form of cancer for which there is a strong need to find, establish, and standardize new, alternative therapies is colorectal cancer. This review discusses some of the factors, including those involved in DC dysfunction, that we believe to be of major influence in DC therapy in colorectal cancer.


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