Approximately half of patients with advanced melanoma do not respond to anti-PD-1, and as such, biomarkers for predicting response/resistance are desirable. PD-1-PD-L1 proximity in the tumor microenvironment has been proposed a biomarker. The impact which cell type is expressing PD-1 and/or PD-L1, expression intensity, hot spot vs whole slide sampling, distance between these molecules optimize ...

Despite the availability of recently developed chemotherapy regimens, survival times for pancreatic cancer patients remain poor. These patients also respond poorly to immune checkpoint blockade therapies (anti-CTLA-4, anti-PD-L1, anti-PD-1), which suggests the presence of additional immunosuppressive mechanisms in the pancreatic tumour microenvironment (TME). CD40 agonist antibodies (αCD40) pro...

Hypothesis The majority of non-small cell lung cancer (NSCLC) patients treated with anti-PD-1/PD-L1 therapy develop either innate or acquired resistance. Across tumor types, the "T cell-inflamed" tumor microenvironment correlates with clinical response to immunotherapy. We hypothesize that clinical characteristics may be predictive of resistance and that "T cell-inflamed" NSCLC tumors can be id...

Platinum-based chemotherapy combined with anti-PD-1 or PD-L1 monoclonal antibodies (mAbs) is now standard first-line therapy for mNSCLC patients without sensitizing driver mutations. Anti-PD-1 and anti-PD-L1 mAbs are considered to be equivalent in efficacy. In the absence of head-to-head randomized control trials (RCTs), we utilized network meta-analysis (NWM) provide an indirect comparison the...

Abstract Precision for Medicine (Precision) has optimized the use of commercial anti-PD-1 and anti-IgG4 reagents to detect both free PD-1 and/or Pembro-bound in pharmacodynamic studies when Pembrolizumab, a concomitant check point inhibitor, is used combination with new therapy. developed qualified flow immunophenotyping assays quantify on CD4+ CD8+ T cells using clone (PD1.3.1.3) an anti-IgG4....

Programmed death-1 receptor (PD-L1, B7-H1) and programmed cell death protein 1 (PD-1) pathway blockade is a promising therapy for treating cancer. However, the mechanistic contribution of host and tumor PD-L1 and PD-1 signaling to the therapeutic efficacy of PD-L1 and PD-1 blockade remains elusive. Here, we evaluated 3 tumor-bearing mouse models that differ in their sensitivity to PD-L1 blockad...

Abstract Summary: Although combination anti–PD-1 and anti-CTLA4 mAbs have revolutionized outcomes for many cancers, their utility has been limited due to significant immune-related toxicities the emergence of resistance. In this issue Cancer Discovery, Dovedi colleagues describe development preclinical testing MEDI5752, a bispecific anti–PD-1/CTLA4 antibody designed optimize therapeutic respons...

Parkinson's disease (PD) is a chronic neurodegenerative condition which has the second largest incidence rate among all other neurodegenerative disorders barring Alzheimer's disease (AD). Currently there is no cure and researchers continue to probe the therapeutic prospect in cell cultures and animal models of PD. Out of several factors contributing to PD prognosis, the role of p38 MAPKs (mitog...

PURPOSE To systematically evaluate the overall efficacy and safety of current anti-PD-1/PD-L1 antibodies for treatment of patients with advanced or refractory cancer. RESULTS Fifty-one trials including 6,800 patients were included. The overall response rates for melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) were 29% (95% CI: 1.53-2.41), 21% (95% CI: 17%-25%) and...

PURPOSE To determine the antitumor efficacy and toxicity of a novel combination approach involving adoptive T-cell immunotherapy using chimeric antigen receptor (CAR) T cells with an immunomodulatory reagent for blocking immunosuppression. EXPERIMENTAL DESIGN We examined whether administration of a PD-1 blocking antibody could increase the therapeutic activity of CAR T cells against two diffe...