Update of early phase clinical trials in cancer immunotherapy

Lee, Dong Hoon

doi:10.5483/bmbrep.2021.54.1.242

Cited by 29 publications

(18 citation statements)

References 100 publications

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“…Finally, there is a phase I/Ib study of NIS793 (antibody against TGF-β) plus PDR001 (spartalizumab, a PD-1 inhibitor) in patients with advanced cancers, including HCC. This potential treatment is based on the fact that TGF-β is Tregs and suppresses the effect of T-helper cells against cancer cells [ 106 , 125 ].…”

Section: Current Immunotherapy In Hepatocellular Carcinomamentioning

confidence: 99%

Immunotherapy as a Therapeutic Strategy for Gastrointestinal Cancer—Current Treatment Options and Future Perspectives

Koustas

Trifylli

Sarantis

et al. 2022

IJMS

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Gastrointestinal (GI) cancer constitutes a highly lethal entity among malignancies in the last decades and is still a major challenge for cancer therapeutic options. Despite the current combinational treatment strategies, including chemotherapy, surgery, radiotherapy, and targeted therapies, the survival rates remain notably low for patients with advanced disease. A better knowledge of the molecular mechanisms that influence tumor progression and the development of optimal therapeutic strategies for GI malignancies are urgently needed. Currently, the development and the assessment of the efficacy of immunotherapeutic agents in GI cancer are in the spotlight of several clinical trials. Thus, several new modalities and combinational treatments with other anti-neoplastic agents have been identified and evaluated for their efficiency in cancer management, including immune checkpoint inhibitors, adoptive cell transfer, chimeric antigen receptor (CAR)-T cell therapy, cancer vaccines, and/or combinations thereof. Understanding the interrelation among the tumor microenvironment, cancer progression, and immune resistance is pivotal for the optimal therapeutic management of all gastrointestinal solid tumors. This review will shed light on the recent advances and future directions of immunotherapy for malignant tumors of the GI system.

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Section: Current Immunotherapy In Hepatocellular Carcinomamentioning

confidence: 99%

Immunotherapy as a Therapeutic Strategy for Gastrointestinal Cancer—Current Treatment Options and Future Perspectives

Koustas

Trifylli

Sarantis

et al. 2022

IJMS

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“…Patients with higher baseline ctDNA levels and persistently high ctDNA levels early during treatment had shorter progression free survival (PFS) and overall survival (OS) [ 58 ]. Reduction of ctDNA levels post 2–3 weeks of ICI administration was predictive of higher OS [ 6 , 56 ]. Researchers from three recent studies, (1) 1/2 CD-ON-MEDI4736-1108 trial (NCT01693562) [ 59 , 61 ], (2) a phase 2 ATLANTIC trial (NCT02087423) [ 62 ], and (3) phase 3 randomized MYSTIC trial (NCT02453282) [ 63 ], where the efficacy of a checkpoint inhibitor therapy durvalumab was tested, with or without tremelimumab, confirmed that the pretreatment ctDNA can be employed as a prognostic biomarker (ctDNA detection suggestive of responsive patient), and that on-treatment ctDNA dynamics could predict immunotherapy success (lower levels of ctDNA on treatment).…”

Section: Circulating Tumor Dna (Ctdna)mentioning

confidence: 99%

“…Despite encouraging results in multiple cancer types, particularly in melanoma [ 3 ], lung cancer [ 4 ], and renal cancer [ 5 ], approximately 40–60% of patients do not achieve any significant therapeutic benefit from IO [ 6 ]. This is perhaps governed by individual germline or cancer specific genetics and further mediated by varying trophic, metabolic, and immunological factors [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…When ICIs re-enable T cell activation, higher TMB results in more neo-antigens, thus increasing the chances for T cell recognition, and clinically correlates with better ICI outcomes [ 15 , 17 ]. However, in some patients with both high TMB and PD-L1 positivity, IO still fails, revealing our incomplete understanding of the factors mediating the response to ICIs [ 6 , 7 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Harnessing Liquid Biopsies to Guide Immune Checkpoint Inhibitor Therapy

Fatima

Safrachi

et al. 2022

Cancers

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Immunotherapy (IO), involving the use of immune checkpoint inhibition, achieves improved response-rates and significant disease-free survival for some cancer patients. Despite these beneficial effects, there is poor predictability of response and substantial rates of innate or acquired resistance, resulting in heterogeneous responses among patients. In addition, patients can develop life-threatening adverse events, and while these generally occur in patients that also show a tumor response, these outcomes are not always congruent. Therefore, predicting a response to IO is of paramount importance. Traditionally, tumor tissue analysis has been used for this purpose. However, minimally invasive liquid biopsies that monitor changes in blood or other bodily fluid markers are emerging as a promising cost-effective alternative. Traditional biomarkers have limitations mainly due to difficulty in repeatedly obtaining tumor tissue confounded also by the spatial and temporal heterogeneity of tumours. Liquid biopsy has the potential to circumvent tumor heterogeneity and to help identifying patients who may respond to IO, to monitor the treatment dynamically, as well as to unravel the mechanisms of relapse. We present here a review of the current status of molecular markers for the prediction and monitoring of IO response, focusing on the detection of these markers in liquid biopsies. With the emerging improvements in the field of liquid biopsy, this approach has the capacity to identify IO-eligible patients and provide clinically relevant information to assist with their ongoing disease management.

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“…Several novel recombinant antibodies have been designed to act as an immune receptor agonist to stimulate an immune response. Utomilumab and Urelumab (PF-05082566) bind to the 4-1BB receptor (CD-137) presented on CD8 + and CD4 + T cells and NK cells, consequently stimulating their activity and increasing proliferation [ 227 ] currently also being tested against HNSCC [ 228 , 229 ]. Figure 6 also summarizes some of these drugs, currently in clinical trials.…”

Section: Targeting Oncogenic Pathways In Hnsccmentioning

confidence: 99%

Shooting at Moving and Hidden Targets—Tumour Cell Plasticity and the Notch Signalling Pathway in Head and Neck Squamous Cell Carcinomas

Kałafut

Czerwonka

Anameriç

et al. 2021

Cancers

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Head and Neck Squamous Cell Carcinoma (HNSCC) is often aggressive, with poor response to current therapies in approximately 40–50% of the patients. Current therapies are restricted to operation and irradiation, often combined with a small number of standard-of-care chemotherapeutic drugs, preferentially for advanced tumour patients. Only very recently, newer targeted therapies have entered the clinics, including Cetuximab, which targets the EGF receptor (EGFR), and several immune checkpoint inhibitors targeting the immune receptor PD-1 and its ligand PD-L1. HNSCC tumour tissues are characterized by a high degree of intra-tumour heterogeneity (ITH), and non-genetic alterations that may affect both non-transformed cells, such as cancer-associated fibroblasts (CAFs), and transformed carcinoma cells. This very high degree of heterogeneity likely contributes to acquired drug resistance, tumour dormancy, relapse, and distant or lymph node metastasis. ITH, in turn, is likely promoted by pronounced tumour cell plasticity, which manifests in highly dynamic and reversible phenomena such as of partial or hybrid forms of epithelial-to-mesenchymal transition (EMT), and enhanced tumour stemness. Stemness and tumour cell plasticity are strongly promoted by Notch signalling, which remains poorly understood especially in HNSCC. Here, we aim to elucidate how Notch signal may act both as a tumour suppressor and proto-oncogenic, probably during different stages of tumour cell initiation and progression. Notch signalling also interacts with numerous other signalling pathways, that may also have a decisive impact on tumour cell plasticity, acquired radio/chemoresistance, and metastatic progression of HNSCC. We outline the current stage of research related to Notch signalling, and how this pathway may be intricately interconnected with other, druggable targets and signalling mechanisms in HNSCC.

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Update of early phase clinical trials in cancer immunotherapy

Cited by 29 publications

References 100 publications

Immunotherapy as a Therapeutic Strategy for Gastrointestinal Cancer—Current Treatment Options and Future Perspectives

Immunotherapy as a Therapeutic Strategy for Gastrointestinal Cancer—Current Treatment Options and Future Perspectives

Harnessing Liquid Biopsies to Guide Immune Checkpoint Inhibitor Therapy

Shooting at Moving and Hidden Targets—Tumour Cell Plasticity and the Notch Signalling Pathway in Head and Neck Squamous Cell Carcinomas

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