Journal: Cancer Medicine

Article Title: PD-1 as a potential target in cancer therapy

doi: 10.1002/cam4.106

Figure Lengend Snippet: PD-1 pathway–targeted agents in development

Article Snippet: Genentech and Roche are evaluating a mAb targeting PD-L1 (RG7446/MPDL3280A), and Amplimmune and GlaxoSmithKline have partnered in the development of a PD-L2/IgG1 fusion protein (AMP-224) that blocks PD-1 signaling.

Techniques:

Journal: Cancer Medicine

Article Title: PD-1 as a potential target in cancer therapy

doi: 10.1002/cam4.106

Figure Lengend Snippet: PD-1 in T-cell activation, exhaustion, and effector function. (A) T cells are activated via (1) binding of MHC plus peptide on an APC to the TCR and then (2) binding of APC CD80/86 to T-cell CD28. In patients with cancer, tumor cells can also serve as APCs. Upon T-cell activation, PD-1 expression is induced. (B) In situations of chronic infection or persistent stimulation, PD-L1 signals through T-cell PD-1 to “turn off” T cells in order to minimize damage to healthy tissue. Tumor cells can upregulate PD-L1 in order to “turn off” T cells that might destroy them. (C) Blocking the PD-1/PD-L1 signaling pathway allows T cells to maintain their effector functions. In patients with cancer, activated tumor-specific T cells can kill tumor cells and secrete cytokines that activate/recruit other immune cells to participate in the antitumor response. APC, antigen-presenting cell; IFN-γ, interferon gamma; MHC, major histocompatibility complex; PD-1, programmed death-1; PD-L1, PD ligand 1; TCR, T-cell receptor.

Article Snippet: Genentech and Roche are evaluating a mAb targeting PD-L1 (RG7446/MPDL3280A), and Amplimmune and GlaxoSmithKline have partnered in the development of a PD-L2/IgG1 fusion protein (AMP-224) that blocks PD-1 signaling.

Techniques: Activation Assay, Binding Assay, Expressing, Infection, Blocking Assay

Journal: Cancer Medicine

Article Title: PD-1 as a potential target in cancer therapy

doi: 10.1002/cam4.106

Figure Lengend Snippet: PD-L1 expression and clinical outcomes in cancer

Article Snippet: Genentech and Roche are evaluating a mAb targeting PD-L1 (RG7446/MPDL3280A), and Amplimmune and GlaxoSmithKline have partnered in the development of a PD-L2/IgG1 fusion protein (AMP-224) that blocks PD-1 signaling.

Techniques: Expressing

Journal: Journal of Cancer Research and Clinical Oncology

Article Title: Triple negative breast cancer: approved treatment options and their mechanisms of action

doi: 10.1007/s00432-022-04189-6

Figure Lengend Snippet: Summary of TNBC subtypes, their characteristics and treatments that may be used to treat them

Article Snippet: Atezolizumab: Atezolizumab (brand name: Tecentriq) was developed as an IgG1 monoclonal antibody targeting the protein PD-L1 (programmed cell death-ligand 1) to prevent its interaction with its receptor PD-1, resulting in the reversal of T-cell suppression (Schmid et al. ).

Techniques: Gene Expression, Activation Assay, Expressing, Migration, Immunopeptidomics

Journal: Journal of Cancer Research and Clinical Oncology

Article Title: Triple negative breast cancer: approved treatment options and their mechanisms of action

doi: 10.1007/s00432-022-04189-6

Figure Lengend Snippet: Mechanism of action of the anti-cancer activity of immunotherapeutics. The interaction of the receptor PD-1 with its ligand PD-L1 normally reduces inflammatory response. Tumour cells use this interaction to suppress anti-cancer T-cell response. Inhibition of either the receptor PD-1 (using pembrolizumab) or the ligand PD-L1 (using atezolizumab) results in the activation of the immune response against the tumour cells

Article Snippet: Atezolizumab: Atezolizumab (brand name: Tecentriq) was developed as an IgG1 monoclonal antibody targeting the protein PD-L1 (programmed cell death-ligand 1) to prevent its interaction with its receptor PD-1, resulting in the reversal of T-cell suppression (Schmid et al. ).

Techniques: Activity Assay, Inhibition, Activation Assay

Journal: Cancer

Article Title: Immunotherapy of Head and Neck Cancer: Emerging Clinical Trials From a National Cancer Institute Head and Neck Cancer Steering Committee Planning Meeting

doi: 10.1002/cncr.30449

Figure Lengend Snippet: Immunotherapeutic Agents

Article Snippet: Ongoing pharmaceutical-sponsored trials include the investigation of an anti-killer-cell immunoglobulin-like receptor MoAb in combination with the anti-CTLA-4 MoAb ipilimumab ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01750580","term_id":"NCT01750580"}} NCT01750580 ) or the anti-PD-1 MoAb nivolumab ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01714739","term_id":"NCT01714739"}} NCT01714739 ). table ft1 table-wrap mode="anchored" t5 TABLE 2 caption a7 Drug Mechanism Enhancing ADCC IL-12 (NCI) Cytokine agonist of NK cell activation IL-15 (NCI) Cytokine agonist of NK cell activation VTX-2337 TLR 8 agonist; enhanced DC activation andh IL-12 secretion Lirilumab (Bristol-Myers Squibb) Anti-KIR MoAb 1-7F9 (Innate) Anti-KIR MoAb Targeting immunosuppressive cytokines Siltuximab Anti-IL-6 MoAb CAT-192 Anti-TGF-β MoAb T-cell costimulatory agonists CP-870,893 (Pfizer) CD40 agonist MoAb OX40 MoAb (AgonOx; Providence Health) OX40 agonist MoAb Urelumab (Bristol-Myers Squibb) CD137 agonist MoAb PF-05082566 (Pfizer) CD137 agonist MoAb IMP321 (Immutep) Recombinant soluble dimeric LAG-3 T-cell immune checkpoint inhibitors Ipilimumab (Bristol-Myers Squibb) Anti-CTLA-4 MoAb Tremelimumab (AstraZeneca/Medimmune) Anti-CTLA-4 MoAb Nivolumab (Bristol-Myers Squibb) Anti-PD-1 MoAb Pembrolizumab (Merck) Anti-PD-1 MoAb Durvalumab (MEDI-4736 (AstraZeneca/Medimmune) Anti-PD-L1 MoAb MPDL3280A (Genentech) Anti-PD-L1 MoAb MSB0010718C (EMD-Serono) Anti-PD-L1 MoAb AUNP12 (peptide) (Pierre Fabre/Aurigene) Anti-PD-L1 peptide BMS-986016 (Bristol-Myers Squibb) Anti-LAG-3 MoAb INCB024360 (Incyte) Orally available inhibitor of indoleamine 2,3-dioxygenase (IDO1) Open in a separate window Abbreviations: ADCC, antibody-dependent cell-mediated cytotoxicity; CTLA-4, cytotoxic T-lymphocyte antigen 4; DC, dendritic cells; IL, interleukin; KIR, killer inhibitor receptor; LAG-3, lymphocyte-activation protein 3; MoAb, monoclonal antibody; NCI, National Cancer Institute; NK, natural killer; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; TGF-β, tumor growth factor-β; TLR, toll-like receptor.

Techniques: Activation Assay, Recombinant

Journal: Cancer

Article Title: Immunotherapy of Head and Neck Cancer: Emerging Clinical Trials From a National Cancer Institute Head and Neck Cancer Steering Committee Planning Meeting

doi: 10.1002/cncr.30449

Figure Lengend Snippet: Working Group 1. Window immunotherapy biomarker study followed by definitive chemoradiotherapy (CRT) plus human papillomavirus (HPV) vaccine, anti-programmed death 1 (PD-1)/PD-ligand 1 axis (PD1/PL1) monoclonal antibody (mAb), or both in patients with T4 or N3, HPV-positive (+) oropharynx cancer. CT indicates computed tomography; DDP, cisplatin; Gy, grays; HNSCC, head and neck squamous cell carcinoma; PD-L1, programmed death-ligand 1; PULA, previously untreated, locally advanced; TME, tumor microenvironment.

Article Snippet: Ongoing pharmaceutical-sponsored trials include the investigation of an anti-killer-cell immunoglobulin-like receptor MoAb in combination with the anti-CTLA-4 MoAb ipilimumab ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01750580","term_id":"NCT01750580"}} NCT01750580 ) or the anti-PD-1 MoAb nivolumab ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01714739","term_id":"NCT01714739"}} NCT01714739 ). table ft1 table-wrap mode="anchored" t5 TABLE 2 caption a7 Drug Mechanism Enhancing ADCC IL-12 (NCI) Cytokine agonist of NK cell activation IL-15 (NCI) Cytokine agonist of NK cell activation VTX-2337 TLR 8 agonist; enhanced DC activation andh IL-12 secretion Lirilumab (Bristol-Myers Squibb) Anti-KIR MoAb 1-7F9 (Innate) Anti-KIR MoAb Targeting immunosuppressive cytokines Siltuximab Anti-IL-6 MoAb CAT-192 Anti-TGF-β MoAb T-cell costimulatory agonists CP-870,893 (Pfizer) CD40 agonist MoAb OX40 MoAb (AgonOx; Providence Health) OX40 agonist MoAb Urelumab (Bristol-Myers Squibb) CD137 agonist MoAb PF-05082566 (Pfizer) CD137 agonist MoAb IMP321 (Immutep) Recombinant soluble dimeric LAG-3 T-cell immune checkpoint inhibitors Ipilimumab (Bristol-Myers Squibb) Anti-CTLA-4 MoAb Tremelimumab (AstraZeneca/Medimmune) Anti-CTLA-4 MoAb Nivolumab (Bristol-Myers Squibb) Anti-PD-1 MoAb Pembrolizumab (Merck) Anti-PD-1 MoAb Durvalumab (MEDI-4736 (AstraZeneca/Medimmune) Anti-PD-L1 MoAb MPDL3280A (Genentech) Anti-PD-L1 MoAb MSB0010718C (EMD-Serono) Anti-PD-L1 MoAb AUNP12 (peptide) (Pierre Fabre/Aurigene) Anti-PD-L1 peptide BMS-986016 (Bristol-Myers Squibb) Anti-LAG-3 MoAb INCB024360 (Incyte) Orally available inhibitor of indoleamine 2,3-dioxygenase (IDO1) Open in a separate window Abbreviations: ADCC, antibody-dependent cell-mediated cytotoxicity; CTLA-4, cytotoxic T-lymphocyte antigen 4; DC, dendritic cells; IL, interleukin; KIR, killer inhibitor receptor; LAG-3, lymphocyte-activation protein 3; MoAb, monoclonal antibody; NCI, National Cancer Institute; NK, natural killer; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; TGF-β, tumor growth factor-β; TLR, toll-like receptor.

Techniques: Biomarker Assay, Computed Tomography

Journal: Cancer

Article Title: Immunotherapy of Head and Neck Cancer: Emerging Clinical Trials From a National Cancer Institute Head and Neck Cancer Steering Committee Planning Meeting

doi: 10.1002/cncr.30449

Figure Lengend Snippet: Working Group 2. Randomized, phase 2 study of adjuvant cisplatin and radiotherapy with or without antiprogrammed death-ligand 1 (PD-L1) monoclonal antibody (mAb) in patients with high-risk, human papillomavirus (HPV)-negative (−) head and neck cancer with window correlatives. CRT indicates chemoradiotherapy; CT, computed tomography; DFS, disease-free survival; ECOG, Eastern Cooperative Oncology Group; IMRT, intensity-modulated radiotherapy; PD1/L1, programmed death 1 (PD-1)/PD-ligand 1 axis; TME, tumor microenvironment.

Article Snippet: Ongoing pharmaceutical-sponsored trials include the investigation of an anti-killer-cell immunoglobulin-like receptor MoAb in combination with the anti-CTLA-4 MoAb ipilimumab ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01750580","term_id":"NCT01750580"}} NCT01750580 ) or the anti-PD-1 MoAb nivolumab ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01714739","term_id":"NCT01714739"}} NCT01714739 ). table ft1 table-wrap mode="anchored" t5 TABLE 2 caption a7 Drug Mechanism Enhancing ADCC IL-12 (NCI) Cytokine agonist of NK cell activation IL-15 (NCI) Cytokine agonist of NK cell activation VTX-2337 TLR 8 agonist; enhanced DC activation andh IL-12 secretion Lirilumab (Bristol-Myers Squibb) Anti-KIR MoAb 1-7F9 (Innate) Anti-KIR MoAb Targeting immunosuppressive cytokines Siltuximab Anti-IL-6 MoAb CAT-192 Anti-TGF-β MoAb T-cell costimulatory agonists CP-870,893 (Pfizer) CD40 agonist MoAb OX40 MoAb (AgonOx; Providence Health) OX40 agonist MoAb Urelumab (Bristol-Myers Squibb) CD137 agonist MoAb PF-05082566 (Pfizer) CD137 agonist MoAb IMP321 (Immutep) Recombinant soluble dimeric LAG-3 T-cell immune checkpoint inhibitors Ipilimumab (Bristol-Myers Squibb) Anti-CTLA-4 MoAb Tremelimumab (AstraZeneca/Medimmune) Anti-CTLA-4 MoAb Nivolumab (Bristol-Myers Squibb) Anti-PD-1 MoAb Pembrolizumab (Merck) Anti-PD-1 MoAb Durvalumab (MEDI-4736 (AstraZeneca/Medimmune) Anti-PD-L1 MoAb MPDL3280A (Genentech) Anti-PD-L1 MoAb MSB0010718C (EMD-Serono) Anti-PD-L1 MoAb AUNP12 (peptide) (Pierre Fabre/Aurigene) Anti-PD-L1 peptide BMS-986016 (Bristol-Myers Squibb) Anti-LAG-3 MoAb INCB024360 (Incyte) Orally available inhibitor of indoleamine 2,3-dioxygenase (IDO1) Open in a separate window Abbreviations: ADCC, antibody-dependent cell-mediated cytotoxicity; CTLA-4, cytotoxic T-lymphocyte antigen 4; DC, dendritic cells; IL, interleukin; KIR, killer inhibitor receptor; LAG-3, lymphocyte-activation protein 3; MoAb, monoclonal antibody; NCI, National Cancer Institute; NK, natural killer; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; TGF-β, tumor growth factor-β; TLR, toll-like receptor.

Techniques: Computed Tomography

Journal: Cancer

Article Title: Immunotherapy of Head and Neck Cancer: Emerging Clinical Trials From a National Cancer Institute Head and Neck Cancer Steering Committee Planning Meeting

doi: 10.1002/cncr.30449

Figure Lengend Snippet: Working Group 3. A randomized phase 2 study of stereotactic body radiosurgery (SBRT) plus antiprogrammed death 1 (PD-1)/PD-ligand 1 axis (PD1/L1) monoclonal antibody (mAb) versus antiprogrammed death-ligand 1 (PD1/L1) mAb alone for oligometastatic head and neck cancer. Gy indicates grays; HNSCC, head and neck squamous cell carcinoma; IV, intravenously; q, every; TME, tumor microenvironment.

Article Snippet: Ongoing pharmaceutical-sponsored trials include the investigation of an anti-killer-cell immunoglobulin-like receptor MoAb in combination with the anti-CTLA-4 MoAb ipilimumab ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01750580","term_id":"NCT01750580"}} NCT01750580 ) or the anti-PD-1 MoAb nivolumab ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01714739","term_id":"NCT01714739"}} NCT01714739 ). table ft1 table-wrap mode="anchored" t5 TABLE 2 caption a7 Drug Mechanism Enhancing ADCC IL-12 (NCI) Cytokine agonist of NK cell activation IL-15 (NCI) Cytokine agonist of NK cell activation VTX-2337 TLR 8 agonist; enhanced DC activation andh IL-12 secretion Lirilumab (Bristol-Myers Squibb) Anti-KIR MoAb 1-7F9 (Innate) Anti-KIR MoAb Targeting immunosuppressive cytokines Siltuximab Anti-IL-6 MoAb CAT-192 Anti-TGF-β MoAb T-cell costimulatory agonists CP-870,893 (Pfizer) CD40 agonist MoAb OX40 MoAb (AgonOx; Providence Health) OX40 agonist MoAb Urelumab (Bristol-Myers Squibb) CD137 agonist MoAb PF-05082566 (Pfizer) CD137 agonist MoAb IMP321 (Immutep) Recombinant soluble dimeric LAG-3 T-cell immune checkpoint inhibitors Ipilimumab (Bristol-Myers Squibb) Anti-CTLA-4 MoAb Tremelimumab (AstraZeneca/Medimmune) Anti-CTLA-4 MoAb Nivolumab (Bristol-Myers Squibb) Anti-PD-1 MoAb Pembrolizumab (Merck) Anti-PD-1 MoAb Durvalumab (MEDI-4736 (AstraZeneca/Medimmune) Anti-PD-L1 MoAb MPDL3280A (Genentech) Anti-PD-L1 MoAb MSB0010718C (EMD-Serono) Anti-PD-L1 MoAb AUNP12 (peptide) (Pierre Fabre/Aurigene) Anti-PD-L1 peptide BMS-986016 (Bristol-Myers Squibb) Anti-LAG-3 MoAb INCB024360 (Incyte) Orally available inhibitor of indoleamine 2,3-dioxygenase (IDO1) Open in a separate window Abbreviations: ADCC, antibody-dependent cell-mediated cytotoxicity; CTLA-4, cytotoxic T-lymphocyte antigen 4; DC, dendritic cells; IL, interleukin; KIR, killer inhibitor receptor; LAG-3, lymphocyte-activation protein 3; MoAb, monoclonal antibody; NCI, National Cancer Institute; NK, natural killer; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; TGF-β, tumor growth factor-β; TLR, toll-like receptor.

Techniques:

Journal: Cancer

Article Title: Immunotherapy of Head and Neck Cancer: Emerging Clinical Trials From a National Cancer Institute Head and Neck Cancer Steering Committee Planning Meeting

doi: 10.1002/cncr.30449

Figure Lengend Snippet: Potential Therapeutic Targets in Head & Neck Squamous Cell Carcinoma (HNSCC)

Article Snippet: Ongoing pharmaceutical-sponsored trials include the investigation of an anti-killer-cell immunoglobulin-like receptor MoAb in combination with the anti-CTLA-4 MoAb ipilimumab ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01750580","term_id":"NCT01750580"}} NCT01750580 ) or the anti-PD-1 MoAb nivolumab ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01714739","term_id":"NCT01714739"}} NCT01714739 ). table ft1 table-wrap mode="anchored" t5 TABLE 2 caption a7 Drug Mechanism Enhancing ADCC IL-12 (NCI) Cytokine agonist of NK cell activation IL-15 (NCI) Cytokine agonist of NK cell activation VTX-2337 TLR 8 agonist; enhanced DC activation andh IL-12 secretion Lirilumab (Bristol-Myers Squibb) Anti-KIR MoAb 1-7F9 (Innate) Anti-KIR MoAb Targeting immunosuppressive cytokines Siltuximab Anti-IL-6 MoAb CAT-192 Anti-TGF-β MoAb T-cell costimulatory agonists CP-870,893 (Pfizer) CD40 agonist MoAb OX40 MoAb (AgonOx; Providence Health) OX40 agonist MoAb Urelumab (Bristol-Myers Squibb) CD137 agonist MoAb PF-05082566 (Pfizer) CD137 agonist MoAb IMP321 (Immutep) Recombinant soluble dimeric LAG-3 T-cell immune checkpoint inhibitors Ipilimumab (Bristol-Myers Squibb) Anti-CTLA-4 MoAb Tremelimumab (AstraZeneca/Medimmune) Anti-CTLA-4 MoAb Nivolumab (Bristol-Myers Squibb) Anti-PD-1 MoAb Pembrolizumab (Merck) Anti-PD-1 MoAb Durvalumab (MEDI-4736 (AstraZeneca/Medimmune) Anti-PD-L1 MoAb MPDL3280A (Genentech) Anti-PD-L1 MoAb MSB0010718C (EMD-Serono) Anti-PD-L1 MoAb AUNP12 (peptide) (Pierre Fabre/Aurigene) Anti-PD-L1 peptide BMS-986016 (Bristol-Myers Squibb) Anti-LAG-3 MoAb INCB024360 (Incyte) Orally available inhibitor of indoleamine 2,3-dioxygenase (IDO1) Open in a separate window Abbreviations: ADCC, antibody-dependent cell-mediated cytotoxicity; CTLA-4, cytotoxic T-lymphocyte antigen 4; DC, dendritic cells; IL, interleukin; KIR, killer inhibitor receptor; LAG-3, lymphocyte-activation protein 3; MoAb, monoclonal antibody; NCI, National Cancer Institute; NK, natural killer; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; TGF-β, tumor growth factor-β; TLR, toll-like receptor.

Techniques: Inhibition, Activity Assay

Journal: Cancer

Article Title: Immunotherapy of Head and Neck Cancer: Emerging Clinical Trials From a National Cancer Institute Head and Neck Cancer Steering Committee Planning Meeting

doi: 10.1002/cncr.30449

Figure Lengend Snippet: Immunotherapeutic Agents

Article Snippet: Ongoing pharmaceutical-sponsored trials include the investigation of an anti-killer-cell immunoglobulin-like receptor MoAb in combination with the anti-CTLA-4 MoAb ipilimumab ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01750580","term_id":"NCT01750580"}} NCT01750580 ) or the anti-PD-1 MoAb nivolumab ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01714739","term_id":"NCT01714739"}} NCT01714739 ). table ft1 table-wrap mode="anchored" t5 TABLE 2 caption a7 Drug Mechanism Enhancing ADCC IL-12 (NCI) Cytokine agonist of NK cell activation IL-15 (NCI) Cytokine agonist of NK cell activation VTX-2337 TLR 8 agonist; enhanced DC activation andh IL-12 secretion Lirilumab (Bristol-Myers Squibb) Anti-KIR MoAb 1-7F9 (Innate) Anti-KIR MoAb Targeting immunosuppressive cytokines Siltuximab Anti-IL-6 MoAb CAT-192 Anti-TGF-β MoAb T-cell costimulatory agonists CP-870,893 (Pfizer) CD40 agonist MoAb OX40 MoAb (AgonOx; Providence Health) OX40 agonist MoAb Urelumab (Bristol-Myers Squibb) CD137 agonist MoAb PF-05082566 (Pfizer) CD137 agonist MoAb IMP321 (Immutep) Recombinant soluble dimeric LAG-3 T-cell immune checkpoint inhibitors Ipilimumab (Bristol-Myers Squibb) Anti-CTLA-4 MoAb Tremelimumab (AstraZeneca/Medimmune) Anti-CTLA-4 MoAb Nivolumab (Bristol-Myers Squibb) Anti-PD-1 MoAb Pembrolizumab (Merck) Anti-PD-1 MoAb Durvalumab (MEDI-4736 (AstraZeneca/Medimmune) Anti-PD-L1 MoAb MPDL3280A (Genentech) Anti-PD-L1 MoAb MSB0010718C (EMD-Serono) Anti-PD-L1 MoAb AUNP12 (peptide) (Pierre Fabre/Aurigene) Anti-PD-L1 peptide BMS-986016 (Bristol-Myers Squibb) Anti-LAG-3 MoAb INCB024360 (Incyte) Orally available inhibitor of indoleamine 2,3-dioxygenase (IDO1) Open in a separate window Abbreviations: ADCC, antibody-dependent cell-mediated cytotoxicity; CTLA-4, cytotoxic T-lymphocyte antigen 4; DC, dendritic cells; IL, interleukin; KIR, killer inhibitor receptor; LAG-3, lymphocyte-activation protein 3; MoAb, monoclonal antibody; NCI, National Cancer Institute; NK, natural killer; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; TGF-β, tumor growth factor-β; TLR, toll-like receptor.

Techniques: Activation Assay, Recombinant

Journal: Cancer

Article Title: Immunotherapy of Head and Neck Cancer: Emerging Clinical Trials From a National Cancer Institute Head and Neck Cancer Steering Committee Planning Meeting

doi: 10.1002/cncr.30449

Figure Lengend Snippet: Correlative Biomarkers for Cancer Immunotherapy

Article Snippet: Ongoing pharmaceutical-sponsored trials include the investigation of an anti-killer-cell immunoglobulin-like receptor MoAb in combination with the anti-CTLA-4 MoAb ipilimumab ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01750580","term_id":"NCT01750580"}} NCT01750580 ) or the anti-PD-1 MoAb nivolumab ( ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT01714739","term_id":"NCT01714739"}} NCT01714739 ). table ft1 table-wrap mode="anchored" t5 TABLE 2 caption a7 Drug Mechanism Enhancing ADCC IL-12 (NCI) Cytokine agonist of NK cell activation IL-15 (NCI) Cytokine agonist of NK cell activation VTX-2337 TLR 8 agonist; enhanced DC activation andh IL-12 secretion Lirilumab (Bristol-Myers Squibb) Anti-KIR MoAb 1-7F9 (Innate) Anti-KIR MoAb Targeting immunosuppressive cytokines Siltuximab Anti-IL-6 MoAb CAT-192 Anti-TGF-β MoAb T-cell costimulatory agonists CP-870,893 (Pfizer) CD40 agonist MoAb OX40 MoAb (AgonOx; Providence Health) OX40 agonist MoAb Urelumab (Bristol-Myers Squibb) CD137 agonist MoAb PF-05082566 (Pfizer) CD137 agonist MoAb IMP321 (Immutep) Recombinant soluble dimeric LAG-3 T-cell immune checkpoint inhibitors Ipilimumab (Bristol-Myers Squibb) Anti-CTLA-4 MoAb Tremelimumab (AstraZeneca/Medimmune) Anti-CTLA-4 MoAb Nivolumab (Bristol-Myers Squibb) Anti-PD-1 MoAb Pembrolizumab (Merck) Anti-PD-1 MoAb Durvalumab (MEDI-4736 (AstraZeneca/Medimmune) Anti-PD-L1 MoAb MPDL3280A (Genentech) Anti-PD-L1 MoAb MSB0010718C (EMD-Serono) Anti-PD-L1 MoAb AUNP12 (peptide) (Pierre Fabre/Aurigene) Anti-PD-L1 peptide BMS-986016 (Bristol-Myers Squibb) Anti-LAG-3 MoAb INCB024360 (Incyte) Orally available inhibitor of indoleamine 2,3-dioxygenase (IDO1) Open in a separate window Abbreviations: ADCC, antibody-dependent cell-mediated cytotoxicity; CTLA-4, cytotoxic T-lymphocyte antigen 4; DC, dendritic cells; IL, interleukin; KIR, killer inhibitor receptor; LAG-3, lymphocyte-activation protein 3; MoAb, monoclonal antibody; NCI, National Cancer Institute; NK, natural killer; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; TGF-β, tumor growth factor-β; TLR, toll-like receptor.

Techniques: Imaging, Immunohistochemistry-IF, Activation Assay, RNA Sequencing Assay

Journal: Cell Death & Disease

Article Title: PD-1 protects expanding human T cells from premature restimulation-induced cell death by modulating TCR and CD28 signaling

doi: 10.1038/s41419-026-08530-6

Figure Lengend Snippet: T cells isolated from healthy human donors were activated with anti-CD3/28 beads and IL-2 was added on Day 3. A PD-1, PD-L1, and PD-L2 expression were measured via flow cytometry over 15 days for N = 8 in CD4+ and N = 5 in CD8 + T cells. B Day 4 purified CD8 + T cells were restimulated with autologous irradiated PBMC and anti-CD3 (1 μg/mL) ± anti-CD28 (1 μg/mL) in the presence of control antibody, anti-PD-1, or anti-PD-L1 at 10 μg/mL for 20 hr. Death was assessed via flow cytometry by propidium iodide staining. Single dot correlates with one human donor. Connecting line compares change in untreated and treated samples within the same donor. N = 3. C Diagram illustrating the proxy APC (pAPC) design created with a 1:1:1 ratio of anti-CD3, anti-CD28, and IgG1κ or recombinant human Fc-chimera PD-L1. D Freshly isolated CD4+ or CD8+ human T cells were activated at a 1:1 cell:bead ratio with IgG or PD-L1 beads and monitored via flow cytometry for CD69 expression after 24 hr ( N = 3 CD4 + , N = 5 CD8 + ) and CD25 expression after 72 hr ( N = 3 CD4 + , N = 6 CD8 + ). E Blastogenesis patterns of unactivated, IgG, or PD-L1 activated cells on Day 3 are demonstrated by dot plots assessing forward scatter (FSC) (x-axis) and side scatter (SSC) (y-axis). The progressive changes in FSC monitored via flow cytometry over 3 days are summarized for CD4+ and CD8 + T cells. N = 3 CD4 + , N = 5 CD8 + .

Article Snippet: Blocking antibodies including anti-PD-1 mAb (clone: EH12.2H7, Biolegend, #329926; clone: Pembrolizumab, Selleck, #A2005), anti-PD-L1 mAb (clone: Atezolizumab, BioXCell, #SIM0009), and anti-FASL (clone: NOK-1, Biolegend, 306416) were added to cultures 1 hr prior to TCR restimulation at a final concentration of 10 μg/mL.

Techniques: Isolation, Expressing, Flow Cytometry, Purification, Irradiation, Control, Staining, Recombinant

Journal: Cell Death & Disease

Article Title: PD-1 protects expanding human T cells from premature restimulation-induced cell death by modulating TCR and CD28 signaling

doi: 10.1038/s41419-026-08530-6

Figure Lengend Snippet: A CD8+ or CD4 + T cells were restimulated on Day 4 or Day 11 with p328-IgG of p328-L1 beads at a 1:1 bead:cell ratio and monitored for cell loss via flow cytometry 24 hr later using propidium iodide. N = 8 CD4+ early, N = 11 CD4+ late, N = 9 CD8+ early, N = 18 CD8+ late. B The difference in % cell loss between p328-IgG and p328-L1 beads in ( A ) is plotted for each donor, cell type, and cell stage evaluated. (same N as ( A ). C RICD assays set-up in ( A ) were examined on the flow cytometer using propidium iodide to calculate the percentage of live cells remaining after 24 hr of restimulation. N = 7 CD4+ early, N = 9 CD4+ late, N = 12 CD8+ early, N = 8 CD8+ late. D PD-L1 dose response was determined using the standard RICD setup amd a new bead set that gradually decreased PD-L1 concentration on the bead from 33% to 0%. Day 4 CD4+ and CD8 + T cells were utilized in this experiment. N = 12 CD4 + , N = 10 CD8 + , statistical analysis was calculated with two-way ANOVA. E Diagram representing RICD setup and creation of secondary bead set that was ligated 100% to IgG1κ (control secondary bead) or 67% IgG1κ and 33% recombinant PD-L1, matching the PD-L1 protein concentration on the p328-L1 primary bead. F Day 4 CD8+ and CD4 + T cells were restimulated with a 2:1 bead:cell ratio comprising a 1:1 ratio of the primary bead and 1:1 ratio of the secondary bead. RICD was monitored as in ( A ) N = 12.

Article Snippet: Blocking antibodies including anti-PD-1 mAb (clone: EH12.2H7, Biolegend, #329926; clone: Pembrolizumab, Selleck, #A2005), anti-PD-L1 mAb (clone: Atezolizumab, BioXCell, #SIM0009), and anti-FASL (clone: NOK-1, Biolegend, 306416) were added to cultures 1 hr prior to TCR restimulation at a final concentration of 10 μg/mL.

Techniques: Flow Cytometry, Concentration Assay, Control, Recombinant, Protein Concentration

Journal: Cell Death & Disease

Article Title: PD-1 protects expanding human T cells from premature restimulation-induced cell death by modulating TCR and CD28 signaling

doi: 10.1038/s41419-026-08530-6

Figure Lengend Snippet: A Representative histogram of data displaying demarcation of AnnexinV hi cells -/+ bead restimulation. B Day 4 and Day 11 CD4+ and CD8 + T cells were left unstimulated or were restimulated with p328-IgG or p328-L1 beads for 6 hr before being stained with AnnexinV and propidium iodide and read on the flow cytometer. N = 6. C Representative flow cytometric histogram of PI cell cycle phases based on DNA content. D Day 4 and Day 11 CD4+ and CD8 + T cells were left unstimulated or were restimulated with p328-IgG or p328-L1 beads for 18 hr before being permeabilized and stained with propidium iodide to determine % of cells in the subG1 phase. N = 8 CD4+ early, N = 8 CD4+ late, N = 10 CD8+ early, N = 9 CD8+ late. E Analysis using gated cells from ( D ) was performed to quantify changes in the G1 phase. F Cell phase characterization from ( D ) was analyzed to determine the PD-L1 induced difference in subG1 and G1 phases.

Article Snippet: Blocking antibodies including anti-PD-1 mAb (clone: EH12.2H7, Biolegend, #329926; clone: Pembrolizumab, Selleck, #A2005), anti-PD-L1 mAb (clone: Atezolizumab, BioXCell, #SIM0009), and anti-FASL (clone: NOK-1, Biolegend, 306416) were added to cultures 1 hr prior to TCR restimulation at a final concentration of 10 μg/mL.

Techniques: Staining, Flow Cytometry

Journal: Cell Death & Disease

Article Title: PD-1 protects expanding human T cells from premature restimulation-induced cell death by modulating TCR and CD28 signaling

doi: 10.1038/s41419-026-08530-6

Figure Lengend Snippet: A CD8+ or CD4 + T cells were restimulated on Day 4 with soluble anti-CD3 (OKT3) at 100 ng/mL or anti-CD3/CD28 coated beads at a 1:1 bead:cell ratio. Cell loss/apoptosis was quantified 18–24 hr later after propidium iodide staining and flow cytometry. N = 5 CD4+ early, N = 6 CD4+ late, N = 5 CD8+ early, N = 6 CD8+ late. B Day 4 and Day 11 CD4+ and CD8 + T cells from N = 5 individual donors were stained for CD28 and PD-1 expression and compared via flow cytometry. C Diagram illustrating restimulation beads conjugated with or without anti-CD28, with p328-IgG used to maintain total protein concentration. D CD8+ or CD4 + T cells were restimulated on Day 4 with beads illustrated in ( C ) at a 1:1 bead:cell ratio, monitored for cell loss 24 hr later using propidium iodide using flow cytometry. E The difference in cell loss induced by restimulation with beads -/+ anti-CD28 (leaving anti-CD3 + /- PD-L1-Fc constant) was plotted for every donor ( N = 10).

Article Snippet: Blocking antibodies including anti-PD-1 mAb (clone: EH12.2H7, Biolegend, #329926; clone: Pembrolizumab, Selleck, #A2005), anti-PD-L1 mAb (clone: Atezolizumab, BioXCell, #SIM0009), and anti-FASL (clone: NOK-1, Biolegend, 306416) were added to cultures 1 hr prior to TCR restimulation at a final concentration of 10 μg/mL.

Techniques: Staining, Flow Cytometry, Expressing, Protein Concentration

Journal: Cell Death & Disease

Article Title: PD-1 protects expanding human T cells from premature restimulation-induced cell death by modulating TCR and CD28 signaling

doi: 10.1038/s41419-026-08530-6

Figure Lengend Snippet: A Day 4 CD4+ and CD8 + T cells ( N = 4 donors each) were restimulated with p328-IgG or p328-L1 beads at a 1:1 bead:cell ratio for 5 hr prior to lysate collection. Control cells were left unstimulated or treated with 1 μM STX. After cell lysis and protein standardization, donor lysates were pooled for each stimulation condition and analyzed on the apoptosis protein array. Representative spots for differentially expressed proteins are shown. Protein signal intensity from membrane imaging was analyzed and normalized using QuickSpots software. T cells were restimulated as in ( A ), lysed in RIPA buffer and separated by SDS-PAGE to quantify FASL ( B ) and survivin ( C ). Data are representative of experiments for 3–4 separate donors. ( D ) Day 4 CD4+ and CD8 + T cells were treated with 10 μg/mL anti-FASL blocking antibody for 1 hr prior to restimulation with the quad bead set. Cells were restimulated for 24 hr and stained with propidium iodide; % viability was assessed by flow cytometry. N = 7 CD4 + , N = 5 CD8 + .

Article Snippet: Blocking antibodies including anti-PD-1 mAb (clone: EH12.2H7, Biolegend, #329926; clone: Pembrolizumab, Selleck, #A2005), anti-PD-L1 mAb (clone: Atezolizumab, BioXCell, #SIM0009), and anti-FASL (clone: NOK-1, Biolegend, 306416) were added to cultures 1 hr prior to TCR restimulation at a final concentration of 10 μg/mL.

Techniques: Control, Lysis, Protein Array, Membrane, Imaging, Software, SDS Page, Blocking Assay, Staining, Flow Cytometry