Browsing by Author "Maecker, Holden T"

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    A model for harmonizing flow cytometry in clinical trials.
    (Nat Immunol, 2010-11) Maecker, Holden T; McCoy, J Philip; FOCIS Human Immunophenotyping Consortium; Amos, Michael; Elliott, John; Gaigalas, Adolfas; Wang, Lili; Aranda, Richard; Banchereau, Jacques; Boshoff, Chris; Braun, Jonathan; Korin, Yael; Reed, Elaine; Cho, Judy; Hafler, David; Davis, Mark; Fathman, C Garrison; Robinson, William; Denny, Thomas; Weinhold, Kent; Desai, Bela; Diamond, Betty; Gregersen, Peter; Di Meglio, Paola; Nestle, Frank O; Peakman, Mark; Villanova, Federica; Ferbas, John; Field, Elizabeth; Kantor, Aaron; Kawabata, Thomas; Komocsar, Wendy; Lotze, Michael; Nepom, Jerry; Ochs, Hans; O'Lone, Raegan; Phippard, Deborah; Plevy, Scott; Rich, Stephen; Roederer, Mario; Rotrosen, Dan; Yeh, Jung-Hua
    Complexities in sample handling, instrument setup and data analysis are barriers to the effective use of flow cytometry to monitor immunological parameters in clinical trials. The novel use of a central laboratory may help mitigate these issues.
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    SITC cancer immunotherapy resource document: a compass in the land of biomarker discovery.
    (Journal for immunotherapy of cancer, 2020-12) Hu-Lieskovan, Siwen; Bhaumik, Srabani; Dhodapkar, Kavita; Grivel, Jean-Charles JB; Gupta, Sumati; Hanks, Brent A; Janetzki, Sylvia; Kleen, Thomas O; Koguchi, Yoshinobu; Lund, Amanda W; Maccalli, Cristina; Mahnke, Yolanda D; Novosiadly, Ruslan D; Selvan, Senthamil R; Sims, Tasha; Zhao, Yingdong; Maecker, Holden T
    Since the publication of the Society for Immunotherapy of Cancer's (SITC) original cancer immunotherapy biomarkers resource document, there have been remarkable breakthroughs in cancer immunotherapy, in particular the development and approval of immune checkpoint inhibitors, engineered cellular therapies, and tumor vaccines to unleash antitumor immune activity. The most notable feature of these breakthroughs is the achievement of durable clinical responses in some patients, enabling long-term survival. These durable responses have been noted in tumor types that were not previously considered immunotherapy-sensitive, suggesting that all patients with cancer may have the potential to benefit from immunotherapy. However, a persistent challenge in the field is the fact that only a minority of patients respond to immunotherapy, especially those therapies that rely on endogenous immune activation such as checkpoint inhibitors and vaccination due to the complex and heterogeneous immune escape mechanisms which can develop in each patient. Therefore, the development of robust biomarkers for each immunotherapy strategy, enabling rational patient selection and the design of precise combination therapies, is key for the continued success and improvement of immunotherapy. In this document, we summarize and update established biomarkers, guidelines, and regulatory considerations for clinical immune biomarker development, discuss well-known and novel technologies for biomarker discovery and validation, and provide tools and resources that can be used by the biomarker research community to facilitate the continued development of immuno-oncology and aid in the goal of durable responses in all patients.
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    Vaccine-induced memory CD8+ T cells provide clinical benefit in HER2 expressing breast cancer: a mouse to human translational study.
    (Clinical cancer research : an official journal of the American Association for Cancer Research, 2019-01-11) Crosby, Erika J; Gwin, William; Blackwell, Kimberly; Marcom, Paul K; Chang, Serena; Maecker, Holden T; Broadwater, Gloria; Hyslop, Terry; Kim, Sungjin; Rogatko, Andre; Lubkov, Veronica; Snyder, Joshua C; Osada, Takuya; Hobeika, Amy C; Morse, Michael A; Lyerly, H Kim; Hartman, Zachary C
    PURPOSE:Immune-based therapy for metastatic breast cancer has had limited success, particularly in molecular subtypes with low somatic mutations rates. Strategies to augment T cell infiltration of tumors include vaccines targeting established oncogenic drivers like the genomic amplification of HER2. We constructed a vaccine based on a novel alphaviral vector encoding a portion of HER2 (VRP-HER2). EXPERIMENTAL DESIGN:In preclinical studies, mice were immunized with VRP-HER2 before or after implantation of hHER2+ tumor cells and HER2-specific immune responses and anti-tumor function were evaluated. We tested VRP-HER2 in a Phase I clinical trial where subjects with advanced HER2-overexpressing malignancies in cohort 1 received VRP-HER2 every 2 weeks for a total of three doses. In cohort 2, subjects received the same schedule concurrently with a HER2-targeted therapy. RESULTS:Vaccination in preclinical models with VRP-HER2 induced HER2-specific T cells and antibodies while inhibiting tumor growth. VRP-HER2 was well tolerated in patients and vaccination induced HER2-specific T cells and antibodies. Although a phase I study, there was one partial response and two patients with continued stable disease. Median OS was 50.2 months in cohort 1 (n=4) and 32.7 months in cohort 2 (n=18). Perforin expression by memory CD8 T cells post-vaccination significantly correlated with improved PFS. CONCLUSIONS:VRP-HER2 increased HER2-specific memory CD8 T cells and had anti-tumor effects in preclinical and clinical studies. The expansion of HER2-specific memory CD8 T cells in vaccinated patients was significantly correlated with increased PFS. Subsequent studies will seek to enhance T cell activity by combining with anti-PD-1.