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  1. Article ; Online: Exercise as an Immune Boost: Mechanism-Driven Support for Lifestyle Interventions.

    Betof Warner, Allison

    Cancer immunology research

    2023  Volume 11, Issue 9, Page(s) 1158

    Abstract: Modifiable host factors have demonstrated promise to enhance responses to immunotherapy. In this issue, Savage et al. investigated the use of aerobic exercise to enhance antitumor immunity in a murine model of melanoma. They show that treadmill running ... ...

    Abstract Modifiable host factors have demonstrated promise to enhance responses to immunotherapy. In this issue, Savage et al. investigated the use of aerobic exercise to enhance antitumor immunity in a murine model of melanoma. They show that treadmill running improves tumor vasculature and alters both T-cell and myeloid-cell infiltration of the tumor via an ERK5-dependent mechanism, adding to the growing evidence supporting the immune-mediated antitumor effects of exercise. See related article by Savage et al., p. 1168 (3).
    MeSH term(s) Humans ; Mice ; Animals ; Phosphorylation ; CD8-Positive T-Lymphocytes/immunology ; Melanoma/immunology ; Immunotherapy ; Life Style ; Tumor Microenvironment
    Language English
    Publishing date 2023-08-08
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2732489-8
    ISSN 2326-6074 ; 2326-6066
    ISSN (online) 2326-6074
    ISSN 2326-6066
    DOI 10.1158/2326-6066.CIR-23-0585
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: CD4+ TIL to the Rescue of Anti-PD-1 Failure by Targeting MHC-II.

    Betof Warner, Allison / Luke, Jason J

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2023  Volume 29, Issue 19, Page(s) 3829–3831

    Abstract: In this CCR Translations, we discuss the potential for tumor-infiltrating lymphocyte therapy to overcome immune checkpoint inhibitor resistance through CD4+-mediated and MHC-II-dependent killing. Validating these results from human tumors has potential ... ...

    Abstract In this CCR Translations, we discuss the potential for tumor-infiltrating lymphocyte therapy to overcome immune checkpoint inhibitor resistance through CD4+-mediated and MHC-II-dependent killing. Validating these results from human tumors has potential to improve the clinical application of adoptive cellular transfer in advanced cancers. See related article by Draghi et al., p. 3937.
    MeSH term(s) Humans ; Lymphocytes, Tumor-Infiltrating/immunology ; Immunotherapy, Adoptive ; Melanoma ; Signal Transduction ; CD4-Positive T-Lymphocytes/immunology
    Language English
    Publishing date 2023-07-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-23-1333
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Tumor-Infiltrating Lymphocyte Therapy in Melanoma: Facts to the Future.

    Betof Warner, Allison / Corrie, Pippa G / Hamid, Omid

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2022  Volume 29, Issue 10, Page(s) 1835–1854

    Abstract: Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) is gaining momentum and demonstrating durable responses in patients with advanced melanoma. Although increasingly considered as a treatment option for select patients with melanoma, TIL ... ...

    Abstract Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) is gaining momentum and demonstrating durable responses in patients with advanced melanoma. Although increasingly considered as a treatment option for select patients with melanoma, TIL therapy is not yet approved by any regulatory agency. Pioneering studies with first-generation TIL therapy, undertaken before the advent of modern melanoma therapeutics, demonstrated clinical efficacy and remarkable long-term overall survival, reaching beyond 20 months for responding patients. TIL therapy is a multistep process of harvesting patient-specific tumor-resident T cells from tumors, ex vivo T-cell expansion, and re-infusion into the same patient after a lymphodepleting preparative regimen, with subsequent supportive IL2 administration. Objective response rates between 30% and 50% have consistently been observed in heavily pretreated patients with metastatic melanoma, including those who have progressed after modern immune checkpoint inhibitors and BRAF targeted agents, a population with high unmet medical need. Although significant strides have been made in modern TIL therapeutics, refinement strategies to optimize patient selection, enhance TIL production, and improve efficacy are being explored. Here, we review past and present experience, current challenges, practical considerations, and future aspirations in the evolution of TIL therapy for the treatment of melanoma as well as other solid tumors.
    MeSH term(s) Humans ; Immunotherapy, Adoptive ; Lymphocytes, Tumor-Infiltrating ; Melanoma/pathology ; Treatment Outcome ; Combined Modality Therapy
    Language English
    Publishing date 2022-12-09
    Publishing country United States
    Document type Review ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-22-1922
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Factors Determining Long-Term Antitumor Responses to Immune Checkpoint Blockade Therapy in Melanoma.

    Loo, Kimberly / Smithy, James W / Postow, Michael A / Betof Warner, Allison

    Frontiers in immunology

    2022  Volume 12, Page(s) 810388

    Abstract: With the increasing promise of long-term survival with immune checkpoint blockade (ICB) therapies, particularly for patients with advanced melanoma, clinicians and investigators are driven to identify prognostic and predictive factors that may help to ... ...

    Abstract With the increasing promise of long-term survival with immune checkpoint blockade (ICB) therapies, particularly for patients with advanced melanoma, clinicians and investigators are driven to identify prognostic and predictive factors that may help to identify individuals who are likely to experience durable benefit. Several ICB combinations are being actively developed to expand the armamentarium of treatments for patients who may not achieve long-term responses to ICB single therapies alone. Thus, negative predictive markers are also of great interest. This review seeks to deepen our understanding of the mechanisms underlying the durability of ICB treatments. We will discuss the currently available long-term data from the ICB clinical trials and real-world studies describing the survivorship of ICB-treated melanoma patients. Additionally, we explore the current treatment outcomes in patients rechallenged with ICB and the patterns of ICB resistance based on sites of disease, namely, liver or CNS metastases. Lastly, we discuss the landscape in melanoma in the context of prognostic or predictive factors as markers of long-term response to ICB.
    MeSH term(s) Animals ; Biomarkers, Tumor ; Clinical Trials as Topic ; Disease Management ; Disease Susceptibility ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Immune Checkpoint Proteins/genetics ; Immune Checkpoint Proteins/metabolism ; Melanoma/drug therapy ; Melanoma/etiology ; Melanoma/metabolism ; Melanoma/mortality ; Molecular Targeted Therapy/adverse effects ; Molecular Targeted Therapy/methods ; Prognosis ; Treatment Outcome
    Chemical Substances Biomarkers, Tumor ; Immune Checkpoint Inhibitors ; Immune Checkpoint Proteins
    Language English
    Publishing date 2022-01-11
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.810388
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Adoptive Cell Transfer and Vaccines in Melanoma: The Horizon Comes Into View.

    Betof-Warner, Allison / Sullivan, Ryan J / Sarnaik, Amod

    American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

    2021  Volume 42, Page(s) 1–8

    Abstract: Over the past four decades, cancer immunotherapy for melanoma has evolved from single-agent, type-I cytokine therapy to combination immune checkpoint inhibition. Along the way, breakthroughs in the fields of cell therapy and cancer vaccination have been ... ...

    Abstract Over the past four decades, cancer immunotherapy for melanoma has evolved from single-agent, type-I cytokine therapy to combination immune checkpoint inhibition. Along the way, breakthroughs in the fields of cell therapy and cancer vaccination have been made as well. The early data from adoptive cell therapy, involving the delivery of tumor infiltrating lymphocytes harvested from resected tumors, was generated at the National Cancer Institute. Subsequently, a limited number of centers across the globe have developed programs to deliver these therapies. Recently, more widespread availability of this therapy has been made possible by centralizing the growth and expansion of tumor infiltrating lymphocyte products, then distributing the products for delivery of therapy at numerous academic medical centers. Work is ongoing to optimize these treatments with additional cell types and/or modified cell products, and to determine the best ways of combining these treatments with immune checkpoint inhibition. Similarly, tumor vaccination strategies are undergoing dramatic changes, transitioning the field from peptide-based vaccines to next-generation sequencing and T-cell receptor sequencing. These changes help improve the selection of targeted antigens by finding more immunogenic options, and they help with the development of lipid nanoparticles and mRNA delivery. In short, evolution of the approaches that are revolutionizing infectious disease vaccination has been ongoing, and there are promising preliminary data in patients with melanoma.
    MeSH term(s) Adoptive Transfer ; Cancer Vaccines/therapeutic use ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Immunotherapy, Adoptive ; Liposomes ; Melanoma/genetics ; Nanoparticles
    Chemical Substances Cancer Vaccines ; Immune Checkpoint Inhibitors ; Lipid Nanoparticles ; Liposomes
    Language English
    Publishing date 2021-09-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2431126-1
    ISSN 1548-8756 ; 1548-8748
    ISSN (online) 1548-8756
    ISSN 1548-8748
    DOI 10.1200/EDBK_351114
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Efficacy of immunotherapy for melanoma brain metastases in patients with concurrent corticosteroid exposure.

    Tringale, Kathryn R / Reiner, Anne S / Sehgal, Ryka R / Panageas, Katherine / Betof Warner, Allison S / Postow, Michael A / Moss, Nelson S

    CNS oncology

    2023  Volume 12, Issue 1, Page(s) CNS93

    Abstract: Aim: ...

    Abstract Aim:
    MeSH term(s) Humans ; Retrospective Studies ; Melanoma/drug therapy ; Brain Neoplasms ; Immunotherapy/methods ; Adrenal Cortex Hormones/therapeutic use
    Chemical Substances Adrenal Cortex Hormones
    Language English
    Publishing date 2023-02-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2692808-5
    ISSN 2045-0915 ; 2045-0915
    ISSN (online) 2045-0915
    ISSN 2045-0915
    DOI 10.2217/cns-2022-0014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Real-world treatment patterns and outcomes for patients with advanced melanoma treated with immunotherapy or targeted therapy.

    Lee, Sejin / Bennett, Antonia V / Zhou, Xi / Betof Warner, Allison / Trogdon, Justin G / Kent, Erin E / Lund, Jennifer L

    Pharmacoepidemiology and drug safety

    2023  Volume 32, Issue 9, Page(s) 988–1000

    Abstract: Objective: To identify real-world patterns of first line treatment, treatment sequence and outcomes for older adults diagnosed with advanced melanoma who received immunotherapy or targeted therapy.: Methods: The study population included older adults ...

    Abstract Objective: To identify real-world patterns of first line treatment, treatment sequence and outcomes for older adults diagnosed with advanced melanoma who received immunotherapy or targeted therapy.
    Methods: The study population included older adults (ages 65+) diagnosed with unresectable or metastatic melanoma between 2012 and 2017 and who received first line immunotherapy or targeted therapy. Using the linked surveillance, epidemiology, and end results-medicare data, we described patterns of first line treatment and treatment sequence through 2018. We used descriptive statistics to report patient and provider characteristics by first line treatment receipt and changes in first line therapy use over calendar time. We also described overall survival (OS) and time to treatment failure (TTF) by first line treatment using the Kaplan-Meier method. For patterns of treatment sequence, we reported commonly observed treatment switch patterns by treatment sub-category and calendar year.
    Results: The analyses included 584 patients (mean age = 76.3 years). A majority (n = 502) received first line immunotherapy. There was a sustained increase in immunotherapy uptake, most notably from 2015 to 2016. The estimated median OS and TTF were longer with first line immunotherapy than with targeted therapy. Individuals treated with CTLA-4 + PD-1 inhibitors had the longest median OS (28.4 months). The most common treatment switch pattern was from a first line CTLA-4 inhibitor to a second line PD-1 inhibitor.
    Conclusions: Our findings inform understanding of treatment patterns of currently used immunotherapies and targeted therapies in older adults with advanced melanoma. Immunotherapy use has increased steadily with PD-1 inhibitors becoming a dominant treatment option since 2015.
    MeSH term(s) Humans ; Aged ; United States/epidemiology ; Immune Checkpoint Inhibitors/therapeutic use ; Treatment Outcome ; Medicare ; Melanoma/drug therapy ; Immunotherapy ; Retrospective Studies
    Chemical Substances Immune Checkpoint Inhibitors
    Language English
    Publishing date 2023-04-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1099748-9
    ISSN 1099-1557 ; 1053-8569
    ISSN (online) 1099-1557
    ISSN 1053-8569
    DOI 10.1002/pds.5630
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Expert consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy.

    Betof Warner, Allison / Hamid, Omid / Komanduri, Krishna / Amaria, Rodabe / Butler, Marcus O / Haanen, John / Nikiforow, Sarah / Puzanov, Igor / Sarnaik, Amod / Bishop, Michael R / Schoenfeld, Adam J

    Journal for immunotherapy of cancer

    2024  Volume 12, Issue 2

    Abstract: Adoptive cell therapy with autologous, ex vivo-expanded, tumor-infiltrating lymphocytes (TILs) is being investigated for treatment of solid tumors and has shown robust responses in clinical trials. Based on the encouraging efficacy, tolerable safety ... ...

    Abstract Adoptive cell therapy with autologous, ex vivo-expanded, tumor-infiltrating lymphocytes (TILs) is being investigated for treatment of solid tumors and has shown robust responses in clinical trials. Based on the encouraging efficacy, tolerable safety profile, and advancements in a central manufacturing process, lifileucel is now the first US Food and Drug Administration (FDA)-approved TIL cell therapy product. To this end, treatment management and delivery practice guidance is needed to ensure successful integration of this modality into clinical care. This review includes clinical and toxicity management guidelines pertaining to the TIL cell therapy regimen prepared by the TIL Working Group, composed of internationally recognized hematologists and oncologists with expertize in TIL cell therapy, and relates to patient care and operational aspects. Expert consensus recommendations for patient management, including patient eligibility, screening tests, and clinical and toxicity management with TIL cell therapy, including tumor tissue procurement surgery, non-myeloablative lymphodepletion, TIL infusion, and IL-2 administration, are discussed in the context of potential standard of care TIL use. These recommendations provide practical guidelines for optimal clinical management during administration of the TIL cell therapy regimen, and recognition of subsequent management of toxicities. These guidelines are focused on multidisciplinary teams of physicians, nurses, and stakeholders involved in the care of these patients.
    MeSH term(s) United States ; Humans ; Immunotherapy, Adoptive ; Lymphocytes, Tumor-Infiltrating/pathology ; Melanoma/pathology ; Combined Modality Therapy ; Cell- and Tissue-Based Therapy
    Language English
    Publishing date 2024-02-29
    Publishing country England
    Document type Review ; Journal Article
    ZDB-ID 2719863-7
    ISSN 2051-1426 ; 2051-1426
    ISSN (online) 2051-1426
    ISSN 2051-1426
    DOI 10.1136/jitc-2023-008735
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Another Victory for Immune Checkpoint Blockade in Melanoma: Adjuvant Ipilimumab Over Interferon.

    Betof Warner, Allison / Postow, Michael A

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2019  Volume 38, Issue 6, Page(s) 529–531

    MeSH term(s) Humans ; Interferon alpha-2 ; Ipilimumab ; Melanoma ; Nivolumab ; United States
    Chemical Substances Interferon alpha-2 ; Ipilimumab ; Nivolumab (31YO63LBSN)
    Language English
    Publishing date 2019-12-27
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.19.02988
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Real-world outcomes of different lines and sequences of treatment in BRAF-positive advanced melanoma patients.

    Betof Warner, Allison / Tarhini, Ahmad / Kang, Barinder / Nakasato, Antonio / Ling, You-Li / Shah, Rohan / Tang, Jackson / Patel, Jeetvan

    Melanoma research

    2022  Volume 33, Issue 1, Page(s) 38–49

    Abstract: The objective of this study is to compare efficacy with different treatment sequences and lines of treatment among BRAF V600 mutated (BRAF+) advanced melanoma patients with immunotherapies (IO) and targeted therapies (TT) using real-world data. This was ... ...

    Abstract The objective of this study is to compare efficacy with different treatment sequences and lines of treatment among BRAF V600 mutated (BRAF+) advanced melanoma patients with immunotherapies (IO) and targeted therapies (TT) using real-world data. This was a retrospective cohort study using the Novartis BRAF+ meLanoma patients ObsErvational database, the harmonized customized data from Flatiron and ConcertAI. The study included BRAF+ advanced unresectable melanoma patients treated with first-line (1L) IO or TT between 1 January 2014 and 31 May 2020. Patient characteristics and treatment patterns were described. Kaplan-Meier curves and propensity score-adjusted Cox models were used for analyzing progression-free survival (PFS) and overall survival (OS). A total of 1961 patients were included, of which, 57.2% received IO and 42.8% received TT on 1L therapy. Overall, 603 patients initiated a 2L therapy: 56.2% IO and 43.8% TT. Regardless of treatment sequence, patients progressed at a relatively similar rate with no significant difference between groups (median PFS: 12.9 months for 1L TT/2L IO and 13.1 months for 1L IO/2L TT; HR, 0.84; P = 0.137). The 2-year OS rate was also similar with 1L TT/2L IO and 1L IO/2L TT (78% vs. 80%; HR, 1.09; P = 0.730). PFS was worse on 2L therapy compared with 1L (median 4.7 vs. 6.5 months). Efficacy on 2L therapy was poor compared with 1L. Among patients who received 2L therapy, regardless of treatment sequences, outcomes were comparable between 1L TT/2L IO and 1L IO/2L TT in this study that reflects real-world experiences beyond clinical trial selective eligibility criteria.
    MeSH term(s) Humans ; Melanoma/drug therapy ; Melanoma/genetics ; Proto-Oncogene Proteins B-raf/genetics ; Proto-Oncogene Proteins B-raf/therapeutic use ; Retrospective Studies ; Skin Neoplasms/drug therapy ; Immunotherapy
    Chemical Substances Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; BRAF protein, human (EC 2.7.11.1)
    Language English
    Publishing date 2022-10-15
    Publishing country England
    Document type Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1095779-0
    ISSN 1473-5636 ; 0960-8931
    ISSN (online) 1473-5636
    ISSN 0960-8931
    DOI 10.1097/CMR.0000000000000856
    Database MEDical Literature Analysis and Retrieval System OnLINE

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