PRIMMO study protocol: a phase II study combining PD-1 blockade, radiation and immunomodulation to tackle cervical and uterine cancer

Tuyaerts, Sandra; Nuffel, Van; Naert, Eline; Dam, Peter P.A. Van; Vuylsteke, Peter; Caluwé, Alex De; Aspeslagh, Sandrine; Dirix, Piet; Lippens, Lien; Jaeghere, Emiel De; Amant, Frédéric; Vandecasteele, Katrien; Denys, Hannelore

doi:10.1186/s12885-019-5676-3

Cited by 53 publications

(44 citation statements)

References 50 publications

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“…Other humanized antibodies of checkpoint inhibitors targeting PD-1, such as atezolizumab, durvalumab, tremelimumab, ipilimumab and nivolumab, were also studied in EC with a POLE-ultramutated and MSI-hypermutated phenotype. A significant clinical response was observed in these clinical trials (111,(113)(114)(115)(116). These clinical trials involving immunotherapy for EC are available at https://clinicaltrials.gov, and are listed in Table III.…”

Section: Immunotherapy For Ecmentioning

confidence: 97%

“…These findings suggested that the assessment of an immune response rather than the molecular subtype may better predict a clinical response to immunotherapy (120,121). Nevertheless, as aforementioned, targeting the PD-1 signaling pathway has great potential in enhancing antitumor immune responses, as accumulating evidence demonstrates that antitumor functions are induced following PD-1 and PD-L1 engagement in cancer cells in vivo (50,(112)(113)(114)(115)(116)(117). These multifunctional PD-1 signaling pathways need to be made available for the treatment of additional types of cancer.…”

Section: Immunotherapy For Ecmentioning

confidence: 99%

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Immune disorder in endometrial cancer: Immunosuppressive microenvironment, mechanisms of immune evasion and immunotherapy (Review)

et al. 2020

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Immunotherapy is an emerging clinical approach that has gained traction over the past decade as a novel treatment option for lung cancer and melanoma. Notably, researchers have made marked improvements in the treatment of endometrial cancer (EC), and potential immune responses have been identified in patients with EC, thereby offering the possibility of exploring immunotherapy for EC. Nevertheless, various needs remain unmet, and immunotherapy applications in EC have yielded limited success, as only a minority of patients exhibited a clinical response. Therefore, further understanding of immune dysfunction associated with EC is still required. The present review describes recent findings regarding the immunosuppressive microenvironment of EC, with emphasis on immune evasion mechanisms and immunotherapy in EC.

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Section: Immunotherapy For Ecmentioning

confidence: 97%

Section: Immunotherapy For Ecmentioning

confidence: 99%

Immune disorder in endometrial cancer: Immunosuppressive microenvironment, mechanisms of immune evasion and immunotherapy (Review)

et al. 2020

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“…The primary endpoint is the ORR at week 26 and the secondary endpoints include safety, ORR at week 26, best overall response, PFS, OS, and quality of life. This ongoing trial will end in 2022 [40]. Abbreviations: ORR; overall response rate, PFS; progression-free survival, DFS; disease-free survival, OS; overall survival.…”

Section: Combination Therapy Of Pd-1 Inhibitors With Chemotherapy Andmentioning

confidence: 99%

“…In the phase 2 PRIMMO Study, Tuyaerts et al are evaluating the antitumor efficacy of pembrolizumab in combination with radiotherapy and immunomodulation in UC patients [40]. Patients will receive pembrolizumab over 3 weeks for a total of 6 cycles, with radiation given on days 1, 3, and 5.…”

Section: Combination Therapy With Pd-1 Inhibitorsmentioning

confidence: 99%

The Latest Findings of PD-1/PD-L1 Inhibitor Application in Gynecologic Cancers

Kooshkaki

Derakhshani

Safarpour

et al. 2020

IJMS

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Gynecologic cancers account for approximately 11% of the newly diagnosed cancers in women in the United States and for 18% globally. The presence of tumor-infiltrating lymphocytes (TILs) influences the clinical outcome of cancer patients and immune checkpoint inhibitors (ICIs), including anti programmed cell death protein-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), and anticytotoxic T-lymphocyte antigen 4 (anti-CTLA-4), which have been approved for treating different types of malignancies. Antibodies targeting the PD-1/PD-L1 checkpoint have shown dynamic and durable tumor regressions, suggesting a rebalancing of the host–tumor interaction. There are several the US food and drug administration (FDA)-approved ICIs targeting PD-1, including pembrolizumab and nivolumab, as well as those targeting PD-L1, including avelumab, atezolizumab, and durvalumab for melanoma, renal cell cancer, colorectal cancer, head and neck cancer, cervix cancer, urothelial cancer, and lung cancer. Current pre-clinical and clinical studies assessing PD-1/PD-L1 inhibitors in several gynecologic cancers have reported significant antitumor activity. In this review, we investigate pre-clinical and clinical studies that describe the safety and efficacy of anti-PD-1/PD-L1 antibodies, with a particular focus on ongoing clinical trials, analyzing the oncological outcome and adverse effects of ICIs in gynecologic cancers.

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“…Intra-tumoral injection of caerin 1.1 and 1.9 peptides in vaccinated TC-1 tumour bearing mice with PD-1 blockade modulates macrophage heterogeneity and the activation of CD8+ T cells in the tumour microenvironment cancers, including nearly 100% of cervical cancers 1 . Cervical cancers are the 3 rd most common cancer in women worldwide 2 . Moreover, high risk HPV infection, especially HPV16 infection, is related to a fraction of head and neck epithelial carcinoma in both developed and undeveloped countries 3 .…”

mentioning

confidence: 99%

Intra-tumoral injection of caerin 1.1 and 1.9 peptides in vaccinated TC-1 tumour bearing mice with PD-1 blockade modulates macrophage heterogeneity and the activation of CD8+ T cells in the tumour microenvironment

Ni¹,

Wu²,

Liu³

et al. 2020

Preprint

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Development of a vaccine formula that alters the tumour-infiltrating lymphocytes to be more immune active against a tumour is key to the improvement of clinical responses to immunotherapy. Here, we demonstrate that, in conjunction with E7 antigen specific immunotherapy, and IL-10 and PD-1 blockade, intra-tumoral administration of caerin 1.1 and 1.9 peptides further improves the tumour microenvironment (TME) when compared with injection of a control peptide. We used single cell transcriptomics and mass spectrometry-based proteomics to quantify changes in cellular activity across different cell types within the TME. We show that the injection of caerin 1.1/1.9 increases immune activating macrophages and NK cells, while reducing immunosuppressive macrophages with M2 phenotype, and increased numbers of activated CD8+ T cells with higher populations of memory and effector-memory CD8+ T subsets. Proteomic profiling demonstrated activation of Stat1 modulated apoptosis and production of nitric oxide. Further, computational integration of the proteome with the single cell transcriptome was consistent with deactivation of immune suppressive B cell function following caerin 1.1 and 1.9 treatment.

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PRIMMO study protocol: a phase II study combining PD-1 blockade, radiation and immunomodulation to tackle cervical and uterine cancer

Cited by 53 publications

References 50 publications

Immune disorder in endometrial cancer: Immunosuppressive microenvironment, mechanisms of immune evasion and immunotherapy (Review)

Immune disorder in endometrial cancer: Immunosuppressive microenvironment, mechanisms of immune evasion and immunotherapy (Review)

The Latest Findings of PD-1/PD-L1 Inhibitor Application in Gynecologic Cancers

Intra-tumoral injection of caerin 1.1 and 1.9 peptides in vaccinated TC-1 tumour bearing mice with PD-1 blockade modulates macrophage heterogeneity and the activation of CD8+ T cells in the tumour microenvironment

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