Topic
Ticilimumab
About: Ticilimumab is a research topic. Over the lifetime, 21 publications have been published within this topic receiving 544 citations.
Papers
TL;DR: The immunobiologic effects of ticilimumab, a human monoclonal antibody against CTLA‐4, was administered to patients with metastatic melanoma who participated in a Phase I/II clinical trial.
Abstract: BACKGROUND
T-regulatory (TR) cells expressing cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) maintain peripheral immune tolerance and negatively affect host immune responses against cancer. The immunobiologic effects of ticilimumab, a human monoclonal antibody against CTLA-4, was administered to patients with metastatic melanoma who participated in a Phase I/II clinical trial.
METHODS
Thirty patients who received ticilimumab at a dose of 10 mg/kg monthly (n = 20) or 15 mg/kg every 3 months (n = 10) were studied at study entry and at 14-day intervals thereafter to assess lymphocyte immunophenotypes, interleukin (IL)-2 and IL-10 production, and the expression of TR-related genes in peripheral blood mononuclear cells (PBMC) from a subset of patients was studied by real-time polymerase chain reaction.
RESULTS
Four of 12 patients with immune-related adverse events (IRAE) attained objective antitumor responses (ATR), whereas only 1 of 18 patients without IRAE attained ATR (χ2 = 4.0; P = .0455). Patients with ATR had significant reductions in TR cells and constitutive IL-10 production accompanied by a significant increase in IL-2 production by activated T cells. Although IRAE+/ATR+ patients demonstrated a positive correlation between CTLA-4 and glucocorticoid-induced tumor necrosis factor receptor (GITR) transcripts (Spearman rho = .522; P = .015), IRAE−/ATR− patients had a positive correlation between the transcripts of CTLA-4 and program death-1 (PD-1) receptor (Spearman rho = .891; P = .000).
CONCLUSIONS
Antitumor responses in patients with metastatic melanoma who were treated with ticilimumab were found to be correlated with reductions in TR cells and constitutive secretion of IL-10, an increase in IL-2 production, and a positive correlation between transcripts of CTLA-4 and GITR. Conversely, a lack of ATR was found to be correlated with steady levels of TR cells and constitutive IL-10 secretion, and a positive correlation between the transcripts of CTLA-4 and PD-1. Cancer 2006. © 2006 American Cancer Society.
149 citations
TL;DR: The putative mechanism of action, its preclinical pharmacology and clinical results to date across a range of cancer settings as monotherapy, as well as in combination with other therapies are described.
Abstract: Tremelimumab is an investigational, fully human IgG monoclonal antibody directed against CTLA-4, a coinhibitory receptor that represses effector T-cell activity in cancer. Tremelimumab has produced promising anticancer responses in early clinical trials. However, a phase III trial of tremelimumab monotherapy versus chemotherapy in advanced melanoma was stopped early when no statistically significant difference in overall survival was observed between the two interventions. This article describes tremelimumab's putative mechanism of action, its preclinical pharmacology and clinical results to date across a range of cancer settings as monotherapy, as well as in combination with other therapies. The failure of the Phase III trial in melanoma is examined and factors affecting the possible future clinical development of tremelimumab are also explored.
70 citations
TL;DR: Immunotherapies are developed for melanoma patients in stage IV who have distant metastases and in stage II to III patients in the adjuvant micrometastatic setting, where only a fraction of patients have widespread (microscopic) disease.
Abstract: About 20% of all primary melanomas will spread. The likelihood of metastatic behavior correlates with prognostic factors such as tumor thickness, mitotic index, presence of ulceration, lymphocyte infiltration, age, gender, and anatomic site. Immunotherapies are developed for melanoma patients in stage IV who have distant metastases and in stage II to III patients in the adjuvant micrometastatic setting, where only a fraction of patients have widespread (microscopic) disease.
57 citations
TL;DR: Two monoclonal antibodies blocking CTLA4 have demonstrated ability to break tolerance to self-tissues and result in long lasting objective cancer regressions, and have moved onto late stages of clinical development.
55 citations
TL;DR: This review focuses on HCC immunobiology and on the potential of immune checkpoint blockade therapy for this tumour, with a critical evaluation of the available trials on immune checkpoint blocking antibodies treatment for HCC, and assesses the potential applicability of immune checkpoints inhibitors in the real-life setting by analysing a large, multicentre cohort of Italian patients with HCC.
Abstract: Despite progress in our understanding of the biology of hepatocellular carcinoma (HCC), this tumour remains difficult-to-cure for several reasons, starting from the particular disease environment where it arises—advanced chronic liver disease—to its heterogeneous clinical and biological behaviour. The advent, and good results, of immunotherapy for cancer called for the evaluation of its potential application also in HCC, where there is evidence of intra-hepatic immune response activation. Several studies advanced our knowledge of immune checkpoints expression in HCC, thus suggesting that immune checkpoint blockade may have a strong rationale even in the treatment of HCC. According to this background, initial studies with tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, and nivolumab, a programmed cell death protein 1 (PD-1) antibody, showed promising results, and further studies exploring the effects of other immune checkpoint inhibitors, alone or with other drugs, are currently underway. However, we are still far from the identification of the correct setting, and sequence, where these drugs might be used in clinical practice, and their actual applicability in real-life is unknown. This review focuses on HCC immunobiology and on the potential of immune checkpoint blockade therapy for this tumour, with a critical evaluation of the available trials on immune checkpoint blocking antibodies treatment for HCC. Moreover, it assesses the potential applicability of immune checkpoint inhibitors in the real-life setting, by analysing a large, multicentre cohort of Italian patients with HCC.
54 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 2 |
| 2019 | 1 |
| 2014 | 1 |
| 2013 | 1 |
| 2010 | 1 |
| 2009 | 3 |