Paul P. Tak
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View article: 513 Advanced analytics identify a differential immune response to CAN-2409+valacyclovir in non-squamous vs squamous NSCLC, linked to improved survival in patients with progressive ICI-refractory NSCLC
513 Advanced analytics identify a differential immune response to CAN-2409+valacyclovir in non-squamous vs squamous NSCLC, linked to improved survival in patients with progressive ICI-refractory NSCLC Open
View article: 893 Integrative discovery of a multimodal cancer immunotherapy using machine learning and viral vector engineering
893 Integrative discovery of a multimodal cancer immunotherapy using machine learning and viral vector engineering Open
View article: The TNFα-binding domain of the therapeutic antibody adalimumab elicits CD4 T-cell responses in rheumatoid arthritis patients
The TNFα-binding domain of the therapeutic antibody adalimumab elicits CD4 T-cell responses in rheumatoid arthritis patients Open
Treatment efficacy of patients receiving anti-TNF antibodies is limited by the formation of anti-drug antibodies. These are observed in most adalimumab-treated rheumatoid arthritis patients, despite the adjuvant-free and human sequence-der…
View article: 995 Therapeutic potential of CAN-3110 in Ras-Raf pathway altered melanoma
995 Therapeutic potential of CAN-3110 in Ras-Raf pathway altered melanoma Open
View article: 1096 A novel viral immunotherapeutic targeting the CD47/SIRPα axis demonstrates potent anti-tumor effects
1096 A novel viral immunotherapeutic targeting the CD47/SIRPα axis demonstrates potent anti-tumor effects Open
Background The CD47/SIRPα axis mediates a 'don't eat me' signal exploited by tumor cells to escape macrophage-mediated immune surveillance. Anti-CD47 therapies have shown promising clinical results in solid and hematological malignancies; …
View article: 1348 Development of enLIGHTEN™ Alpha-201 herpes simplex viral vectors encoding payloads targeting the tumor microenvironment
1348 Development of enLIGHTEN™ Alpha-201 herpes simplex viral vectors encoding payloads targeting the tumor microenvironment Open
Background Failure to respond to conventional immunotherapies arises from heterogeneous mechanisms present in the tumor microenvironments (TME) that drive resistance in non-responding patients. Candel's enLIGHTEN™ Discovery Platform applie…
View article: 653 Neoadjuvant CAN-2409+Prodrug plus chemoradiation for borderline resectable or locally advanced non-metastatic pancreatic adenocarcinoma (PDAC)
653 Neoadjuvant CAN-2409+Prodrug plus chemoradiation for borderline resectable or locally advanced non-metastatic pancreatic adenocarcinoma (PDAC) Open
Background Effective therapies for PDAC are urgently needed. CAN-2409 is a replication-defective adenovirus encoding the HSV-thymidine kinase gene, administered intratumorally in combination with a prodrug (valacyclovir or acyclovir). Cell…
View article: Clinical trial links oncolytic immunoactivation to survival in glioblastoma
Clinical trial links oncolytic immunoactivation to survival in glioblastoma Open
Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM) 1,2 . Here we report the results of a first-in-human phase I trial in…
View article: Uncovering transcriptomic landscape alterations of CAN-2409 in in vitro and in vivo glioma models
Uncovering transcriptomic landscape alterations of CAN-2409 in in vitro and in vivo glioma models Open
Rationale CAN-2409 is a locally delivered oncolytic therapy, which results in vaccination against the injected tumor. CAN-2409 consists of a non-replicating adenovirus armed with the Herpes virus thymidine kinase, which metabolizes gancicl…
View article: A randomized, phase II study of sequential belimumab and rituximab in primary Sjögren’s syndrome
A randomized, phase II study of sequential belimumab and rituximab in primary Sjögren’s syndrome Open
BACKGROUNDPrimary Sjögren's syndrome (pSS) is characterized by B cell hyperactivity and elevated B-lymphocyte stimulator (BLyS). Anti-BLyS treatment (e.g., belimumab) increases peripheral memory B cells; decreases naive, activated, and pla…
View article: 1477 First efficacy and multi-omic analysis data from phase 1 clinical trial of oncolytic viral immunotherapy with CAN-2409 + valacyclovir in combination with nivolumab and standard of care in newly diagnosed high-grade glioma
1477 First efficacy and multi-omic analysis data from phase 1 clinical trial of oncolytic viral immunotherapy with CAN-2409 + valacyclovir in combination with nivolumab and standard of care in newly diagnosed high-grade glioma Open
Background High-grade glioma (HGG) is characterized by a highly immunosuppressive tumor microenvironment and poor prognosis. Limited advances have been made in HGG standard of care (SoC) treatment, with immunotherapy failures reported in t…
View article: CTIM-09. ENRICHED TCR/BCR VDJ REARRANGEMENTS CORRELATE WITH MRI AND SURVIVAL OUTCOMES IN PATIENTS WITH RECURRENT HIGH-GRADE GLIOMA TREATED WITH CAN-3110
CTIM-09. ENRICHED TCR/BCR VDJ REARRANGEMENTS CORRELATE WITH MRI AND SURVIVAL OUTCOMES IN PATIENTS WITH RECURRENT HIGH-GRADE GLIOMA TREATED WITH CAN-3110 Open
BACKGROUND CAN-3110 (rQNestin34.5v2) is an HSV-1 oncolytic viral immunotherapy with one copy of the inflammatory ICP34.5 gene under transcriptional control of the Nestin glioma-specific promoter. We completed a phase 1 sequential dose-esca…
View article: 1134 Dynamic analyses of tumor microenvironment modulation by CAN-2409 treatment using kaede photoconvertible transgenic mice
1134 Dynamic analyses of tumor microenvironment modulation by CAN-2409 treatment using kaede photoconvertible transgenic mice Open
Background CAN-2409 is a replication-defective adenovirus that delivers the HSV-thymidine kinase gene. Intratumoral administration of CAN-2409 followed by prodrug results in the formation of a toxic metabolite able to induce immunogenic ce…
View article: Synovial gene signatures associated with the development of rheumatoid arthritis in at risk individuals: A prospective study
Synovial gene signatures associated with the development of rheumatoid arthritis in at risk individuals: A prospective study Open
View article: Perturbing DDR signaling enhances cytotoxic effects of local oncolytic virotherapy and modulates the immune environment in glioma
Perturbing DDR signaling enhances cytotoxic effects of local oncolytic virotherapy and modulates the immune environment in glioma Open
View article: Systemic high-dose dexamethasone treatment may modulate the efficacy of intratumoral viral oncolytic immunotherapy in glioblastoma models
Systemic high-dose dexamethasone treatment may modulate the efficacy of intratumoral viral oncolytic immunotherapy in glioblastoma models Open
Background Intratumoral viral oncolytic immunotherapy is a promising new approach for the treatment of a variety of solid cancers. CAN-2409 is a replication-deficient adenovirus that delivers herpes simplex virus thymidine kinase to cancer…
View article: Increased frequency of CD4<sup>+</sup> and CD8<sup>+</sup> follicular helper T cells in human lymph node biopsies during the earliest stages of rheumatoid arthritis
Increased frequency of CD4<sup>+</sup> and CD8<sup>+</sup> follicular helper T cells in human lymph node biopsies during the earliest stages of rheumatoid arthritis Open
Objectives Follicular helper T cells (Tfh cells) provide key B cell help, and are essential in germinal center (GC) formation and (auto) antibody generation. To gain more insight into their role during the earliest phase of rheumatoid arth…
View article: CTIM-13. PHASE 1 CLINICAL TRIAL OF ONCOLYTIC VIRAL IMMUNOTHERAPY WITH CAN-2409 + VALACYCLOVIR IN COMBINATION WITH NIVOLUMAB AND STANDARD OF CARE (SOC) IN NEWLY DIAGNOSED HIGH-GRADE GLIOMA (HGG)
CTIM-13. PHASE 1 CLINICAL TRIAL OF ONCOLYTIC VIRAL IMMUNOTHERAPY WITH CAN-2409 + VALACYCLOVIR IN COMBINATION WITH NIVOLUMAB AND STANDARD OF CARE (SOC) IN NEWLY DIAGNOSED HIGH-GRADE GLIOMA (HGG) Open
BACKGROUND CAN-2409 is a replication-deficient adenovirus that delivers HSV thymidine kinase to cancer cells, resulting in local conversion of orally administered valacyclovir into a toxic metabolite. Previously, a phase 1b/2 clinical tria…
View article: 395 Detection of viral antigen and immune activation after intra-tumor injection of CAN-3110 (ICP-34.5 expressing HSV-1 oncolytic virus) in patients with recurrent high-grade glioma
395 Detection of viral antigen and immune activation after intra-tumor injection of CAN-3110 (ICP-34.5 expressing HSV-1 oncolytic virus) in patients with recurrent high-grade glioma Open
Background Recurrent high-grade glioma (HGG) represents a significant clinical unmet need with expected survival between 6 to 9 months. Oncolytic viruses are a new therapeutic approach for solid tumors that deploy oncolytic activity combin…
View article: A randomised, placebo-controlled study of RIPK1 inhibitor GSK2982772 in patients with active ulcerative colitis
A randomised, placebo-controlled study of RIPK1 inhibitor GSK2982772 in patients with active ulcerative colitis Open
Objective Tumour necrosis factor signalling via the receptor-interacting protein kinase 1 (RIPK1) pathway regulates colonic inflammation suggesting that RIPK1 inhibition may be a potential therapeutic target in ulcerative colitis (UC). Thi…
View article: Novel Insights Into Rheumatoid Arthritis Through Characterization of Concordant Changes in DNA Methylation and Gene Expression in Synovial Biopsies of Patients With Differing Numbers of Swollen Joints
Novel Insights Into Rheumatoid Arthritis Through Characterization of Concordant Changes in DNA Methylation and Gene Expression in Synovial Biopsies of Patients With Differing Numbers of Swollen Joints Open
In this study, we sought to characterize synovial tissue obtained from individuals with arthralgia and disease-specific auto-antibodies and patients with established rheumatoid arthritis (RA), by applying an integrative multi-omics approac…
View article: A randomized, placebo-controlled experimental medicine study of RIPK1 inhibitor GSK2982772 in patients with moderate to severe rheumatoid arthritis
A randomized, placebo-controlled experimental medicine study of RIPK1 inhibitor GSK2982772 in patients with moderate to severe rheumatoid arthritis Open
View article: AB1318-HPR VAGUS NERVE STIMULATION IN PATIENTS WITH RHEUMATOID ARTHRITIS: 48 MONTH SAFETY AND EFFICACY
AB1318-HPR VAGUS NERVE STIMULATION IN PATIENTS WITH RHEUMATOID ARTHRITIS: 48 MONTH SAFETY AND EFFICACY Open
View article: cDC1 are required for the initiation of collagen-induced arthritis
cDC1 are required for the initiation of collagen-induced arthritis Open
View article: Novel Insights into Rheumatoid Arthritis Through Characterisation of Concordant Changes in DNA Methylation and Gene Expression in Synovial Biopsies of Patients with Differing Numbers of Swollen Joints
Novel Insights into Rheumatoid Arthritis Through Characterisation of Concordant Changes in DNA Methylation and Gene Expression in Synovial Biopsies of Patients with Differing Numbers of Swollen Joints Open
View article: Adherence to Treat-to-target Management in Rheumatoid Arthritis and Associated Factors: Data from the International RA BIODAM Cohort
Adherence to Treat-to-target Management in Rheumatoid Arthritis and Associated Factors: Data from the International RA BIODAM Cohort Open
Objective. Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in rheumatoid arthritis (RA). There is limited knowledge regarding the factors that impede implementation of T2T, particularly in a setting where…
View article: Molecular Characterization of Human Lymph Node Stromal Cells During the Earliest Phases of Rheumatoid Arthritis
Molecular Characterization of Human Lymph Node Stromal Cells During the Earliest Phases of Rheumatoid Arthritis Open
Rheumatoid arthritis (RA) is a progressive, destructive autoimmune arthritis. Break of tolerance and formation of autoantibodies occur years before arthritis. Adaptive immunity is initiated in lymphoid tissue where lymph node stromal cells…
View article: Promotion of macrophage activation by Tie2 in the context of the inflamed synovia of rheumatoid arthritis and psoriatic arthritis patients
Promotion of macrophage activation by Tie2 in the context of the inflamed synovia of rheumatoid arthritis and psoriatic arthritis patients Open
Objective To examine the role of Tie2 signalling in macrophage activation within the context of the inflammatory synovial microenvironment present in patients with RA and PsA. Methods Clinical responses and macrophage function were examine…
View article: OP0228 GSK3196165 AN INVESTIGATIONAL ANTI-GM-CSF MONOCLONAL ANTIBODY, IMPROVES PATIENT REPORTED OUTCOMES IN A PHASE IIB STUDY OF PATIENTS WITH RHEUMATOID ARTHRITIS (RA)
OP0228 GSK3196165 AN INVESTIGATIONAL ANTI-GM-CSF MONOCLONAL ANTIBODY, IMPROVES PATIENT REPORTED OUTCOMES IN A PHASE IIB STUDY OF PATIENTS WITH RHEUMATOID ARTHRITIS (RA) Open
View article: Association of response to TNF inhibitors in rheumatoid arthritis with quantitative trait loci for CD40 and CD39
Association of response to TNF inhibitors in rheumatoid arthritis with quantitative trait loci for CD40 and CD39 Open