Identification and characterization of TSR-042, a novel anti-human PD-1 therapeutic antibody

Laken, Haley; Kehry, Marilyn R.; McNeeley, Patricia; Neben, Tamlyn Y.; Zhang, J.; Jenkins, Daniel; Wilcoxen, Keith

doi:10.1016/s0959-8049(16)32902-1

Cited by 24 publications

(17 citation statements)

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“…In addition, TSR-042, a new anti-human PD-1 therapeutic antibody, is in phase I clinical trial stage for the treatment of endometrial cancer. According to the trial data published in October 2018, 13 out of 25 patients with MSI-H had complete or partial remission [ 22 ]. In the present study, the median OS of dMMR patients was not assessed, while the median OS of PMMR patients was 29.2 months in the PD-1 inhibitor combined with the bevacizumab group.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of PD-1 Inhibitor Combined with Bevacizumab in Treatment of Advanced Endometrial Cancer Patients with Mismatch Repair Deficiency (dMMR)/High-Level Microsatellite Instability (MSI-H)

et al. 2022

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Background Mismatch repair deficiency (dMMR) is associated with endometrial cancers, yet it remains unknown how this information could be incorporated into adjuvant treatment paradigms. We performed this cohort study to identify the effect of dMMR status on the prognosis of patients with advanced endometrial cancer treated with PD-1 inhibitor and bevacizumab. Material/Methods We enrolled 93 patients with advanced endometrial cancer and divided them into an observation group (n=52) and a control group (n=41) according to the treatment. The control group was treated with bevacizumab combined with paclitaxel chemotherapy, while the observation group was treated with PD-1inhibitor combined with bevacizumab. The basic characteristics and overall survival times were compared between the 2 groups. Results There was no significant difference in age, course of disease, clinical stage, or pathological type. The proportion of patients with dMMR and high-level microsatellite instability (MSI-H) were balanced in the 2 groups. Patients in the observation group had longer overall survival than those in the control group (33.2 months vs 21.8 months). Moreover, in the observation group, the median OS of dMMR patients was not detected, while the median OS of PMMR patients was 29.2 months ( P <0.01). In the control group, the median OS of dMMR patients was 12.4 months, and that of PMMR patients was 24.1 months ( P <0.01). Conclusions Advanced endometrial cancer patients with dMMR/MSI-H treated with PD-1 inhibitor plus bevacizumab had longer overall survival (OS) than those treated with bevacizumab plus paclitaxel chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Efficacy of PD-1 Inhibitor Combined with Bevacizumab in Treatment of Advanced Endometrial Cancer Patients with Mismatch Repair Deficiency (dMMR)/High-Level Microsatellite Instability (MSI-H)

et al. 2022

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“…Immune checkpoint inhibitors (ICIs), such as anti-programmed death-1 (PD-1) agents are being used increasingly in the treatment of several cancers [ 1 ]. Dostarlimab is an experimental humanized anti-PD-1 immunoglobulin G4 monoclonal antibody against the PD-1 receptor and is under investigational use in clinical trials [ 2 ] and have been a significant advancement in cancer care. ICIs have been associated with immune-related adverse events with a reported incidence of neurological complications in 2–6% [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

Immune checkpoint inhibitor-induced encephalitis with dostarlimab in two patients: Case series

Marzoughi

Chen

2021

eNeurologicalSci

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Immune checkpoint inhibitors (ICIs) are being used increasingly in the treatment of several cancers and have been associated with neurological complications including immune checkpoint inhibitor-induced encephalitis (ICI-iE). We present two cases of ICI-iE with the novel agent dostarlimab, which to our knowledge are the first reported with this agent. These cases add to the growing body of literature on ICI-iE, demonstrating two cases of meningoencephalitis associated with the novel agent dostarlimab treated successfully with prednisone. As imaging studies may be unrevealing, clinicians must maintain a high index of suspicion for ICI-iE in any patient who develops altered mental status on ICI therapy, with low threshold to obtain lumbar puncture for evidence of inflammatory CSF and to exclude other causes. It is important to note that many neurological presentations of ICIs can also be secondary to tumor metastasis and other paraneoplastic syndromes, making the diagnosis challenging. Prognosis can be good with early recognition and treatment with corticosteroids. Whether patients can be rechallenged with ICI is to be determined in larger studies given the rarity of this complication.

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“…In preclinical studies, TSR-022 enhanced the activity of CD4 + T cells isolated from healthy donors [110]. Additionally, TSR-022 did not lead to related local irritation or adverse changes of parameters during either the dosing or recovery phase (doses ≤100 mg/kg).…”

Section: Anti-tim-3 Agents/clinical Studiesmentioning

confidence: 91%

TIM-3 pathway dysregulation and targeting in cancer

Zeidan

Komrokji

Brunner

2021

Expert Review of Anticancer Therapy

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Introduction: Dysfunction of the immune system is a hallmark of cancer. Through increased understanding of the complex interactions between immunity and cancer, immunotherapy has emerged as a treatment modality for different types of cancer. Promising activity with immunotherapy has been reported in numerous malignancies, but challenges such as limited response rates and treatment resistance remain. Furthermore, outcomes with this therapeutic approach in hematologic malignancies are even more limited than in solid tumors. T-cell immunoglobulin domain and mucin domain 3 (TIM-3) has emerged as a potential immune checkpoint target in both solid tumors and hematologic malignancies. TIM-3 has been shown to promote immune tolerance, and overexpression of TIM-3 is associated with more aggressive or advanced disease and poor prognosis.Areas covered: This review examines what is currently known regarding the biology of TIM-3 and clinical implications of targeting TIM-3 in cancer. Particular focus is given to myeloid malignancies. Expert opinion: The targeting of TIM-3 is a promising therapeutic approach in cancers, including hematologic cancers such as myeloid malignancies which have not benefited much from current immunotherapeutic treatment approaches. We anticipate that with further clinical evaluation, TIM-3 blockade will emerge as an important treatment strategy in myeloid malignancies.

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Identification and characterization of TSR-042, a novel anti-human PD-1 therapeutic antibody

Cited by 24 publications

References 0 publications

Efficacy of PD-1 Inhibitor Combined with Bevacizumab in Treatment of Advanced Endometrial Cancer Patients with Mismatch Repair Deficiency (dMMR)/High-Level Microsatellite Instability (MSI-H)

Efficacy of PD-1 Inhibitor Combined with Bevacizumab in Treatment of Advanced Endometrial Cancer Patients with Mismatch Repair Deficiency (dMMR)/High-Level Microsatellite Instability (MSI-H)

Immune checkpoint inhibitor-induced encephalitis with dostarlimab in two patients: Case series

TIM-3 pathway dysregulation and targeting in cancer

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