Immunoediting and persistence of antigen-specific immunity in patients who have previously been vaccinated with NY-ESO-1 protein formulated in ISCOMATRIX™

Nicholaou, Theo; Chen, Weisan; Davis, Ian D.; Jackson, Heather; Dimopoulos, Nektaria; Barrow, Catherine; Browning, Judy; MacGregor, Duncan; Williams, David; Hopkins, Wendie; Maraskovsky, Eugene; Venhaus, Ralph; Pan, Linda; Hoffman, Eric W.; Old, Lloyd J.; Cebon, Jonathan

doi:10.1007/s00262-011-1041-3

Cited by 43 publications

(39 citation statements)

References 24 publications

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“…5 Importantly, our results confirm and extend the results of previously published papers 4,8,24,25 by demonstrating the presence of immunodominant regions of NY-ESO-1 proteins (NY-ESO-1 79-108 and NY-ESO-1 115-138 ), which showed a high level of immunogenicity in a large proportion of vaccinated patients. Of note, it has previously been shown that vaccination strategies based on the injection of recombinant NY-ESO-1 protein in Montanide and CpG resulted in the expansion of NY-ESO-1 specific CD8…”

supporting

confidence: 81%

“…We compared the profile of cytokine production by NY-ESO-1 specific T cells at baseline (i.e., pre-vaccination samples), during the ISCOMA-TRIX priming stage (include Week 5, 9,13) and during the rF-NY-ESO-1 boosting stage (include Week 17,21,25). Supporting Information Figure S4 shows the data from 18 Arm A and 21 Arm B patients stimulated with the NY-ESO-1 peptide pool spanning the full length NY-ESO-1 protein.…”

Section: Poly-functional Cd4mentioning

confidence: 99%

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NY‐ESO‐1 specific antibody and cellular responses in melanoma patients primed with NY‐ESO‐1 protein in ISCOMATRIX and boosted with recombinant NY‐ESO‐1 fowlpox virus

Chen

Dawoodji

Tarlton

et al. 2014

Intl Journal of Cancer

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Vaccination strategies based on repeated injections of NY-ESO-1 protein formulated in ISCOMATRIX particles (NY-ESO-1 ISCOMATRIX) have shown to elicit combined NY-ESO-1 specific antibody and T cell responses. However, it remains unclear whether heterologous prime-boost strategies based on the combination with NY-ESO-1 ISCOMATRIX with different NY-ESO-1 boosting reagents could be used to increase NY-ESO-1 CD8 1 or CD4 1 T cell responses. To address this question, we carried out a randomized clinical trial in 39 high-risk, resected melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX, and then boosted with repeated injections of either recombinant fowlpox virus encoding full length NY-ESO-1 (rF-NY-ESO-1) (Arm A) or NY-ESO-1 ISCOMATRIX alone (Arm B). We have comprehensively analyzed NY-ESO-1 specific T cells and B cells response in all patients before and after vaccination for a total of seven time points per patient. NY-ESO-1 ISCOMATRIX alone elicited a strong NY-ESO-1 specific CD4 1 T cell and antibody response, which was maintained by both regiments at similar levels. Current vaccination strategies based on the use of recombinant viruses are failing to elicit specific T-cell responses similar to those generated by natural infections. The limited success of recombinant viruses as delivery vectors for T cell vaccines is mainly due to their high immunogenicity, resulting in an overwhelming immune response focused on the viral-vector proteins rather than on the desired recombinant protein antigens. 1 However, it remains unclear whether recombinant viruses can be used to boost the magnitude of immune responses elicited by the prior injection of recombinant immunogenic proteins.The cancer-testis antigen NY-ESO-1 is an attractive target antigen for cancer therapy, as it is expressed in many cancer types, but not normal tissues, except testis.2 Although promising results in various NY-ESO-1 formulations have been reported in recent cancer vaccine studies, 3-6 the optimal strategy for generating integrated antibody and T cell responses to control tumor growth has yet to be determined.ISCOMATRIX adjuvant is comprised of saponin, cholesterol and phospholipid and is capable of associating with proteins to form ISCOMATRIX vaccines.7 Recombinant

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supporting

confidence: 81%

Section: Poly-functional Cd4mentioning

confidence: 99%

NY‐ESO‐1 specific antibody and cellular responses in melanoma patients primed with NY‐ESO‐1 protein in ISCOMATRIX and boosted with recombinant NY‐ESO‐1 fowlpox virus

Chen

Dawoodji

Tarlton

et al. 2014

Intl Journal of Cancer

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“…Similarly, T-cell responses were detected in the majority of individuals receiving an HCVcore/ISCOMATRIX vaccine (Drane et al, 2009). Furthermore, similar broad epitope immune responses were generated in cancer patients expressing NY-ESO-1 + tumours and these were sustained for several years (Davis et al, 2004;Ebert et al, 2009;Nicholaou et al, 2011).…”

Section: Iscomatrix Adjuvant Consistently Stimulates Robust and Readimentioning

confidence: 74%

“…This results in both robust and effective Ab and CD8 + T-cell responses. Generation of highfrequency antigen-specific CD8 + T-cell responses is a reproducible feature of ISCOMATRIX vaccines in animals and humans (Davis et al, 2004;Ebert et al, 2009;Drane et al, 2009;Nicholaou et al, 2011), as this is not readily (or weakly at best) detected with other adjuvant systems.…”

Section: Iscomatrix Adjuvant In Prophylactic Vaccinesmentioning

confidence: 99%

ISCOMATRIX: a novel adjuvant for use in prophylactic and therapeutic vaccines against infectious diseases

Morelli

Becher

Koernig

et al. 2012

Journal of Medical Microbiology

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116

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The ISCOMATRIX adjuvant has antigen delivery and presentation properties as well as immunomodulatory capabilities, which combine to provide enhanced and accelerated immune responses. The responses are broad, including a range of subclasses of antibodies as well as CD4+ and CD8 + T-cells. A range of ISCOMATRIX vaccines (ISCOMATRIX adjuvant combined with antigen) have now been tested in clinical trials and have been shown to be generally safe and well tolerated as well as immunogenic, generating both antibody (Ab) and T-cell responses. The mechanisms by which ISCOMATRIX adjuvant facilitates its immune effects are the scope of significant study and indicate that ISCOMATRIX adjuvant (i) rapidly traffics antigen into the cytosol of multiple dendritic cell subsets, (ii) induces the induction of an array of cytokines and chemokines and (iii) links the innate and adaptive immune responses in vivo in a Toll-likereceptor-independent but MyD88-dependent manner. These data highlight the clinical utility of ISCOMATRIX adjuvant in the development of prophylactic and therapeutic vaccines for infectious disease.

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“…However, persisting immune responses are also capable of altering the phenotype of the tumor via a process known as immunoediting or immunosculpting. For example, in patients with melanoma treated with NY-ESO-1 vaccine and immune adjuvant, histologic analysis of tumor samples from patients who relapsed following treatment showed a loss of NY-ESO-1 antigen and human leukocyte antigen expression necessary for immune activation (10,11). This suggests immunoediting selects for tumor variants with little or no immunogenicity and may result in tumor responses to immunotherapies decreasing or reversing over time.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Retreatment with Ipilimumab in Patients with Pretreated Advanced Melanoma Who Progressed after Initially Achieving Disease Control

Robert

Schadendorf

Messina

et al. 2013

Clinical Cancer Research

141

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Purpose: Ipilimumab is a fully human monoclonal antibody against cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) that has been shown to improve survival in patients with pretreated, advanced melanoma in a phase III trial. Some patients in this study who initially responded to ipilimumab treatment but later progressed were eligible for retreatment with their original randomized regimen. Here, outcomes for these patients concerning baseline characteristics, best overall response, and disease control rate are assessed and considered with respect to the overall study population.Experimental Design: In the phase III study, 676 pretreated patients were randomly allocated to treatment with ipilimumab 3 mg/kg plus gp100 vaccine, ipilimumab 3 mg/kg plus placebo, or gp100 vaccine alone. Of these patients, 32 had a partial or complete objective response or stable disease after treatment and met the eligibility criteria for retreatment, although a total of 40 patients were retreated.Results: Best overall response rates (complete responses plus partial responses) for 31 retreatmenteligible patients in the ipilimumab plus gp100 and ipilimumab plus placebo groups were 3 of 23 (13.0%) and 3 of 8 (37.5%), respectively, and disease control rates were 65.2% and 75.0%. No new types of toxicities occurred during retreatment and most events were mild-to-moderate.Conclusion: Ipilimumab provided durable objective responses and/or stable disease in qualifying patients who received retreatment upon disease progression with a similar toxicity profile to that seen during their original treatment regimen.

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Immunoediting and persistence of antigen-specific immunity in patients who have previously been vaccinated with NY-ESO-1 protein formulated in ISCOMATRIX™

Cited by 43 publications

References 24 publications

NY‐ESO‐1 specific antibody and cellular responses in melanoma patients primed with NY‐ESO‐1 protein in ISCOMATRIX and boosted with recombinant NY‐ESO‐1 fowlpox virus

NY‐ESO‐1 specific antibody and cellular responses in melanoma patients primed with NY‐ESO‐1 protein in ISCOMATRIX and boosted with recombinant NY‐ESO‐1 fowlpox virus

ISCOMATRIX: a novel adjuvant for use in prophylactic and therapeutic vaccines against infectious diseases

Efficacy and Safety of Retreatment with Ipilimumab in Patients with Pretreated Advanced Melanoma Who Progressed after Initially Achieving Disease Control

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