Vaccine Strategy in Melanoma

Kwak, Minyoung; Slingluff, Craig L.; Melssen, Marit M.

doi:10.1016/j.soc.2019.02.003

Cited by 19 publications

(16 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34 A number of other vaccines are under evaluation for the treatment of melanoma and may play a role in combination therapy with immune checkpoint inhibitors and/or targeted therapies in the future. 35 At the same time while research into immune checkpoint receptors was being pursued, various tumorigenic mutations were discovered. In particular, BRAF-activating mutations were identified in more than 50% of melanomas and found to play a critical role in driving tumor growth and development.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Evolving impact of long-term survival results on metastatic melanoma treatment

Michielin

Atkins

Koon

et al. 2020

J Immunother Cancer

View full text Add to dashboard Cite

Melanoma treatment has been revolutionized over the past decade. Long-term results with immuno-oncology (I-O) agents and targeted therapies are providing evidence of durable survival for a substantial number of patients. These results have prompted consideration of how best to define long-term benefit and cure. Now more than ever, oncologists should be aware of the long-term outcomes demonstrated with these newer agents and their relevance to treatment decision-making. As the first tumor type for which I-O agents were approved, melanoma has served as a model for other diseases. Accordingly, discussions regarding the value and impact of long-term survival data in patients with melanoma may be relevant in the future to other tumor types. Current findings indicate that, depending on the treatment, over 50% of patients with melanoma may gain durable survival benefit. The best survival outcomes are generally observed in patients with favorable prognostic factors, particularly normal baseline lactate dehydrogenase and/or a low volume of disease. Survival curves from melanoma clinical studies show a plateau at 3 to 4 years, suggesting that patients who are alive at the 3-year landmark (especially in cases in which treatment had been stopped) will likely experience prolonged cancer remission. Quality-of-life and mixture-cure modeling data, as well as metrics such as treatment-free survival, are helping to define the value of this long-term survival. In this review, we describe the current treatment landscape for melanoma and discuss the long-term survival data with immunotherapies and targeted therapies, discussing how to best evaluate the value of long-term survival. We propose that some patients might be considered functionally cured if they have responded to treatment and remained treatment-free for at least 2 years without disease progression. Finally, we consider that, while there have been major advances in the treatment of melanoma in the past decade, there remains a need to improve outcomes for the patients with melanoma who do not experience durable survival.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evolving impact of long-term survival results on metastatic melanoma treatment

Michielin

Atkins

Koon

et al. 2020

J Immunother Cancer

View full text Add to dashboard Cite

show abstract

“…Adjuvants are a critical component in this formulation, and TLR agonists and IFA have shown promise as effective adjuvants in a number of human clinical trials. [33][34][35][36] In a smaller pilot study of the VSME, we found that repeated SSV with peptide plus IFA decreased ARG1 expression, upregulated markers of DC activation and CD40L, supported a Th1-dominant immune response and induced a gene signature associated with formation of TLS in the VSME. 19 The present study validates those prior findings in a larger data set.…”

Section: Discussionmentioning

confidence: 72%

The vaccine-site microenvironment: impacts of antigen, adjuvant, and same-site vaccination on antigen presentation and immune signaling

Meneveau

Kumar

Lynch

et al. 2022

J Immunother Cancer

View full text Add to dashboard Cite

BackgroundA goal of cancer vaccines is to induce strong T cell responses to tumor antigens, but the delivery method, schedule, and formulation of cancer vaccines have not yet been optimized. Adjuvants serve to increase the immune response against vaccine antigens. However, little is known about the impact of adjuvants plus antigen and their delivery schedule on the immunologic milieu in the vaccine-site microenvironment (VSME). We hypothesized that antigen processing and presentation may occur directly in the VSME, that adding the toll-like receptor 3 (TLR3) agonist polyICLC (pICLC) would enhance markers of immune activation, and that the immune signatures would be enhanced further by repeated vaccination in the same skin site rather than after multiple vaccines in different skin locations.MethodsUsing RNA sequencing, we evaluated VSME biopsies from patients undergoing subcutaneous/intradermal peptide vaccination against melanoma, with incomplete Freund’s adjuvant (IFA) with or without pICLC. Differential gene expression analyses and gene set enrichment analyses were performed using R. False discovery rate corrected p values <0.05 were considered significant.ResultsWe found that addition of peptide antigens to IFA enhanced antigen presentation pathways and a tertiary lymphoid structure gene-signature locally at the VSME. Addition of pICLC to IFA + peptide induced an immunologically favorable VSME 1 week after injection but had little impact on the VSME after three injections, compared with IFA + peptide alone. Repeated same-site injection of IFA + peptide antigens induced a VSME with more dendritic cell activation, Th1 dominance, and TLR adaptor protein gene expression than that induced by injections at different, rotating skin locations.ConclusionsThese data suggest that the vaccine-site itself may be a critically important location contributing to vaccine immunity rather than just the draining lymph node, that IFA induces a favorable VSME with TLR agonist being most beneficial early in the vaccine course, and that same-site injections lead to persistent stimulation of immune pathways that may be beneficial in eliciting antigen specific T cell expansion.

show abstract

“…The promise of cancer vaccines is that vaccines induce targeted, tumor-specific immune responses with long-term memory in cases of recurrence or metastasis, with a low risk of toxicity overall. Vaccines may use as an antigen whole tumor cells, RNA or DNA, single or multiple peptides, or APCs displaying the target antigen [ 42 ].…”

Section: Resultsmentioning

confidence: 99%

Emerging Novel Therapeutic Approaches for Treatment of Advanced Cutaneous Melanoma

Comito

Pagani

Grilli

et al. 2022

Cancers

View full text Add to dashboard Cite

The prognosis of patients with advanced cutaneous melanoma has radically changed in the past decade. Nevertheless, primary or acquired resistance to systemic treatment occurs in many cases, highlighting the need for novel treatment strategies. This review has the purpose of summarizing the current area of interest for the treatment of metastatic or unresectable advanced cutaneous melanoma, including data from recently completed or ongoing clinical trials. The main fields of investigation include the identification of new immune checkpoint inhibitors (anti-LAG3, GITR agonist and anti-TIGIT), adoptive cell therapy, vaccines, engineered TCR therapy, IL-2 agonists, novel targets for targeted therapy (new MEK or RAF inhibitors, HDAC, IDO, ERK, Axl, ATR and PARP inhibitors), or combination strategies (antiangiogenetic agents plus immune checkpoint inhibitors, intra-tumoral immunotherapy in combination with systemic therapy). In many cases, only preliminary efficacy data from early phase trials are available, which require confirmation in larger patient cohorts. A more in-depth knowledge of the biological effects of the molecules and identifying predictive biomarkers remain crucial for selecting patient populations most likely to benefit from novel emerging treatment strategies.

show abstract

Vaccine Strategy in Melanoma

Cited by 19 publications

References 80 publications

Evolving impact of long-term survival results on metastatic melanoma treatment

Evolving impact of long-term survival results on metastatic melanoma treatment

The vaccine-site microenvironment: impacts of antigen, adjuvant, and same-site vaccination on antigen presentation and immune signaling

Emerging Novel Therapeutic Approaches for Treatment of Advanced Cutaneous Melanoma

Contact Info

Product

Resources

About