A Pilot Study of Combined Immune Checkpoint Inhibition in combination with ablative therapies in Subjects with Hepatocellular Carcinoma (HCC) - HCC-TACE study

开始日期2020-05-28

申办/合作机构

University College Dublin

100 项与 aptCTLA-4 相关的临床结果

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100 项与 aptCTLA-4 相关的转化医学

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100 项与 aptCTLA-4 相关的专利（医药）

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项与 aptCTLA-4 相关的文献（医药）

2024-12-05·Neuro-Oncology

Intracranial administration of anti-PD-1 and anti-CTLA-4 immune checkpoint-blocking monoclonal antibodies in patients with recurrent high-grade glioma

Article

作者: Lebrun, Laetitia ; Stevens, Latoya ; Salmon, Isabelle ; Vaeyens, Freya ; Vanbinst, Anne-Marie ; Everaert, Hendrik ; Neyns, Bart ; Geeraerts, Xenia ; Tuyaerts, Sandra ; Caljon, Ben ; Dirven, Iris ; Del’haye, Jacomi ; Geens, Wietse ; Bruneau, Michaël ; Duerinck, Johnny ; Kockx, Marc ; Lescrauwaet, Louise ; Brock, Stefanie

AbstractBackgroundRecurrent high-grade glioma (rHGG) lacks effective life-prolonging treatments and the efficacy of systemic PD-1 and CTLA-4 immune checkpoint inhibitors is limited. The multi-cohort Glitipni phase I trial investigates the safety and feasibility of intraoperative intracerebral (iCer) and postoperative intracavitary (iCav) nivolumab (NIVO) ± ipilimumab (IPI) treatment following maximal safe resection (MSR) in rHGG.Materials and methodsPatients received 10 mg IV NIVO within 24 h before surgery, followed by MSR, iCer 5 mg IPI and 10 mg NIVO, and Ommaya catheter placement in the resection cavity. Biweekly postoperative iCav administrations of 1–5–10 mg NIVO (cohort 4) or 10 mg NIVO plus 1–5–10 mg IPI (cohort 7) were combined with 10 mg IV NIVO for 11 cycles.Results42 rHGG patients underwent MSR with iCer NIVO + IPI. 16 pts were treated in cohort 4 (postoperative iCav NIVO at escalating doses) while 28 patients were treated in cohort 7 (intra and postoperative iCav NIVO and escalating doses of IPI). The most common TRAE was fatigue; no grade 5 AE occurred. Dose-limiting toxicity was grade 3 neutrophilic pleocytosis (4 pts) receiving iCav NIVO plus 5 or 10 mg IPI. PFS and OS did not significantly differ between cohorts (median OS: 42 [95% CI 26–57] vs. 35 [29–40] weeks; 1-year OS rate: 37% vs. 29%). Baseline B7–H3 expression significantly correlated with worse survival. OS compared favorably to a historical pooled cohort (n = 469) of Belgian rHGG pts treated with anti-VEGF therapies (log-rank P = .015).ConclusionIntraoperative iCer IPI + NIVO with postoperative iCav NIVO ± IPI up to biweekly doses of 1 mg IPI + 10 mg NIVO is feasible and safe, showing encouraging OS in rHGG patients. ClinicalTrials.gov registration: NCT03233152

2024-11-01·Immunity

T lymphocyte recruitment to melanoma brain tumors depends on distinct venous vessels

Article

作者: Mayer, Chanté D ; Wick, Wolfgang ; Thommek, Calvin ; Berghoff, Anna S. ; Schadendorf, Dirk ; Messmer, Julia M. ; Effern, Maike ; Messmer, Julia M ; Venkataramani, Varun ; Karreman, Matthia A ; Westphal, Dana ; Helfrich, Iris ; Schubert, Marc ; Winkler, Frank ; Wehner, Rebekka ; Hölzel, Michael ; Piechutta, Manuel ; Berghoff, Anna S ; Hinze, Daniel ; Karreman, Matthia A. ; Mayer, Chanté D.

To improve immunotherapy for brain tumors, it is important to determine the principal intracranial site of T cell recruitment from the bloodstream and their intracranial route to brain tumors. Using intravital microscopy in mouse models of intracranial melanoma, we discovered that circulating T cells preferably adhered and extravasated at a distinct type of venous blood vessel in the tumor vicinity, peritumoral venous vessels (PVVs). Other vascular structures were excluded as alternative T cell routes to intracranial melanomas. Anti-PD-1/CTLA-4 immune checkpoint inhibitors increased intracranial T cell motility, facilitating migration from PVVs to the tumor and subsequently inhibiting intracranial tumor growth. The endothelial adhesion molecule ICAM-1 was particularly expressed on PVVs, and, in samples of human brain metastases, ICAM-1 positivity of PVV-like vessels correlated with intratumoral T cell infiltration. These findings uncover a distinct mechanism by which the immune system can access and control brain tumors and potentially influence other brain pathologies.

2023-05-03·Cells

A Mathematical Model for Predicting Patient Responses to Combined Radiotherapy with CTLA-4 Immune Checkpoint Inhibitors

Article

作者: Sung, Wonmo ; Suh, Tae Suk ; Choe, Bo-Young ; Kim, Yongjin

The purpose of this study was to develop a cell-cell interaction model that could predict a tumor's response to radiotherapy (RT) combined with CTLA-4 immune checkpoint inhibition (ICI) in patients with hepatocellular carcinoma (HCC). The previously developed model was extended by adding a new term representing tremelimumab, an inhibitor of CTLA-4. The distribution of the new immune activation term was derived from the results of a clinical trial for tremelimumab monotherapy (NCT01008358). The proposed model successfully reproduced longitudinal tumor diameter changes in HCC patients treated with tremelimumab (complete response = 0%, partial response = 17.6%, stable disease = 58.8%, and progressive disease = 23.6%). For the non-irradiated tumor control group, adding ICI to RT increased the clinical benefit rate from 8% to 32%. The simulation predicts that it is beneficial to start CTLA-4 blockade before RT in terms of treatment sequences. We developed a mathematical model that can predict the response of patients to the combined CTLA-4 blockade with radiation therapy. We anticipate that the developed model will be helpful for designing clinical trials with the ultimate aim of maximizing the efficacy of ICI-RT combination therapy.

100 项与 aptCTLA-4 相关的药物交易

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