Browsing by Author "Bishop, Michael R."

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    The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia
    (BioMed Central, 2016-12-20) Boyiadzis, Michael; Bishop, Michael R.; Abonour, Rafat; Anderson, Kenneth C.; Ansell, Stephen M.; Avigan, David; Barbarotta, Lisa; Barrett, Austin John; Van Besien, Koen; Bergsagel, Leif; Borrello, Ivan; Brody, Joshua; Brufsky, Jill; Cairo, Mitchell; Chari, Ajai; Cohen, Adam; Cortes, Jorge; Forman, Stephen J.; Friedberg, Jonathan W.; Fuchs, Ephraim J.; Gore, Steven D.; Jagannath, Sundar; Kahl, Brad S; Kline, Justin; Kochenderfer, James N.; Kwak, Larry W.; Levy, Ronald; de Lima, Marcos; Litzow, Mark R.; Mahindra, Anuj; Miller, Jeffrey; Munshi, Nikhil C.; Orlowski, Robert Z.; Pagel, John M.; Porter, David L.; Russell, Stephen J.; Schwartz, Karl; Shipp, Margaret A.; Siegel, David; Stone, Richard M.; Tallman, Martin S.; Timmerman, John M.; Van Rhee, Frits; Waller, Edmund K.; Welsh, Ann; Werner, Michael; Wiernik, Peter H.; Dhodapkar, Madhav V.; Department of Medicine, IU School of Medicine
    Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemia. These recommendations were developed following the previously established process based on the Institute of Medicine’s clinical practice guidelines. In doing so, a systematic literature search was performed for high-impact studies from 2004 to 2014 and was supplemented with further literature as identified by the panel. The consensus panel met in December of 2014 with the goal to generate consensus recommendations for the clinical use of immunotherapy in patients with hematologic malignancies. During this meeting, consensus panel voting along with discussion were used to rate and review the strength of the supporting evidence from the literature search. These consensus recommendations focus on issues related to patient selection, toxicity management, clinical endpoints, and the sequencing or combination of therapies. Overall, immunotherapy is rapidly emerging as an effective therapeutic strategy for the management of hematologic malignances. Evidence-based consensus recommendations for its clinical application are provided and will be updated as the field evolves.
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    Two-Stage CD8+ CAR T-Cell Differentiation in Patients with Large B-Cell Lymphoma
    (bioRxiv, 2025-03-15) Cao, Guoshuai; Hu, Yifei; Pan, Tony; Tang, Erting; Asby, Nick; Althaus, Thomas; Wan, Jun; Riedell, Peter A.; Bishop, Michael R.; Kline, Justin P.; Huang, Jun; Medical and Molecular Genetics, School of Medicine
    Chimeric antigen receptor (CAR) T-cell therapy has expanded therapeutic options for patients with diffuse large B-cell lymphoma (DLBCL). However, progress in improving clinical outcomes has been limited by an incomplete understanding of CAR T-cell differentiation in patients. To comprehensively investigate CAR T-cell differentiation in vivo, we performed single-cell, multimodal, and longitudinal analyses of CD28-costimulated CAR T cells from infusion product and peripheral blood (day 8-28) of patients with DLBCL who were successfully treated with axicabtagene ciloleucel. Here, we show that CD8+ CAR T cells undergo two distinct waves of clonal expansion. The first wave is dominated by CAR T cells with an exhausted-like effector memory phenotype during the peak expansion period (day 8-14). The second wave is dominated by CAR T cells with a terminal effector phenotype during the post-peak persistence period (day 21-28). Importantly, the two waves have distinct ontogeny and are biologically uncoupled. Furthermore, lineage tracing analysis via each CAR T cell's endogenous TCR clonotype demonstrates that the two waves originate from different effector precursors in the infusion product. Precursors of the first wave exhibit more effector-like signatures, whereas precursors of the second wave exhibit more stem-like signatures. These findings suggest that pre-infusion heterogeneity mediates the two waves of in vivo clonal expansion. Our findings provide evidence against the intuitive idea that the post-peak contraction in CAR abundance is solely apoptosis or extravasation of short-lived CAR T cells from peak expansion. Rather, our findings demonstrate that CAR T-cell expansion and persistence are mediated by clonally, phenotypically, and ontogenically distinct CAR T-cell populations that serve complementary clinical purposes.