A5008233699- Cancer Immunotherapy and Biomarkers
- Lung Cancer Treatments and Mutations
- Head and Neck Cancer Studies
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- PARP inhibition in cancer therapy
- Radiomics and Machine Learning in Medical Imaging
- Advanced Breast Cancer Therapies
- Ovarian cancer diagnosis and treatment
- Immune Cell Function and Interaction
- Cancer, Stress, Anesthesia, and Immune Response
- Hepatocellular Carcinoma Treatment and Prognosis
- HER2/EGFR in Cancer Research
- Reproductive Biology and Fertility
- Nanoplatforms for cancer theranostics
- Colorectal Cancer Treatments and Studies
- Bladder and Urothelial Cancer Treatments
- Lung Cancer Research Studies
- Lung Cancer Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Immune cells in cancer
- Radiopharmaceutical Chemistry and Applications
- T-cell and B-cell Immunology
AstraZeneca (United Kingdom)
2020-2025
Cambridge Consultants (United Kingdom)
2023
Pfizer (United States)
2018-2022
Arcagy Gineco
2021
AstraZeneca (United States)
2021
Institut Gustave Roussy
2021
Spinal Cord Injury BC
2021
University of Ulsan
2021
Asan Medical Center
2021
Ulsan College
2021
Abstract Radiotherapy is a major part in the treatment of most common cancers, but many patients experience local recurrence with metastatic disease. In evaluating response biomarkers, we found that low doses fractionated radiotherapy led to PD-L1 upregulation on tumor cells variety syngeneic mouse models cancer. Notably, delivered combination αPD-1 or αPD-L1 mAbs generated efficacious CD8+ T-cell responses improved control, long-term survival, and protection against rechallenge. These...
Murine syngeneic tumor models are critical to novel immuno-based therapy development, but the molecular and immunologic features of these still not clearly defined. The translational relevance differences between is fully understood, impeding appropriate preclinical model selection for target validation, ultimately hindering drug development. Across a panel commonly used murine models, we showed variable responsiveness immunotherapies. We array comparative genomic hybridization, whole-exome...
Programmed cell-death 1 ligand (PD-L1) is a member of the B7/CD28 family proteins that control T-cell activation. Many tumors can upregulate expression PD-L1, inhibiting antitumor responses and avoiding immune surveillance elimination. We have identified characterized MEDI4736, human IgG1 monoclonal antibody binds with high affinity specificity to PD-L1 uniquely engineered prevent antibody-dependent cell-mediated cytotoxicity. In vitro assays demonstrate MEDI4736 potent antagonist function,...
Abstract Purpose: Radiotherapy is a highly effective anticancer treatment forming part of the standard care for majority patients, but local and distal disease recurrence remains major cause mortality. known to enhance tumor immunogenicity; however, contribution mechanisms radiotherapy-induced immune responses are unknown. Experimental Design: The impact low-dose fractionated radiotherapy (5 × 2 Gy) alone in combination with αPD-1 mAb on microenvironment was evaluated by flow cytometry...
Although immunotherapy with PD-(L)1 blockade is routine for lung cancer, little known about acquired resistance. Among 1,201 patients non-small cell cancer (NSCLC) treated blockade, resistance common, occurring in >60% of initial responders. Acquired shows differential expression inflammation and interferon (IFN) signaling. Relapsed tumors can be separated by upregulated or stable IFNγ response genes. Upregulation genes associated putative routes characterized signatures persistent IFN...
Abstract Cancer treatment has made significant advancements in recent decades, however many patients still experience failure or resistance. Attempts to identify determinants of response have been hampered by a lack tools that simultaneously accommodate smaller datasets, sparse missing measurements, multimodal clinicogenomic data, and can be interpreted extract biological clinical insights. We introduce the Clinical Transformer, an explainable transformer-based deep-learning framework...
Antibodies targeting T-cell inhibitory pathways, such as CTLA-4 and PD-1/PD-L1, are emerging an important class of cancer therapeutics, a next generation immunomodulatory therapies alternative (e.g. TIM-3, LAG-3, B7-H4, B7-H3, VISTA, A2aR), well co-stimulatory CD27, OX40, GITR, CD137), pathways poised to join them. Most these antibodies IgG isotypes that have low, or no, binding the Fc gamma receptors (FcγRs) trigger cell-mediated cytotoxic effector functions antibody dependent cellular...
1023 Background: Chemotherapy with immune checkpoint inhibitors can improve outcomes vs chemotherapy alone in patients (pts) metastatic TNBC; however, many still have poor clinical outcomes. BEGONIA is an ongoing 2 part, multicenter, multiarm, open-label platform study evaluating safety and efficacy of D (anti–PD-L1)+P D±P combined novel therapies as first-line (1L) treatment for TNBC (NCT03742102). We report initial results from Part 1 Arm 1, D+P, 6, D+T-DXd, antibody-drug conjugate...
Homologous recombination repair gene mutations (HRRm) are common in urothelial carcinoma (UC), rendering tumor cells sensitive to poly (ADP-ribose) polymerase (PARP) inhibition. We assessed efficacy and safety of durvalumab (anti-programmed cell death ligand-1) plus olaparib (PARP inhibitor) patients with metastatic UC (mUC).This randomized, multicenter, double-blind, phase II trial enrolled untreated, platinum-ineligible mUC. Patients (N = 154) were randomly assigned 1:1 receive (1,500 mg...
Abstract Background We explored potential predictive biomarkers of immunotherapy response in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated durvalumab (D) + tremelimumab (T) etoposide-platinum (EP), D EP, or EP the randomized phase 3 CASPIAN trial. Methods 805 treatment-naïve ES-SCLC were (1:1:1) to receive T EP. The primary endpoint was overall survival (OS). Patients required provide an archived tumor tissue block (or ≥ 15 newly cut unstained slides) at screening,...
The development of targeted therapies and immunotherapies has markedly advanced the treatment metastasized melanoma. While with selective BRAF(V600E) inhibitors (like vemurafenib or dabrafenib) leads to high response rates but short duration, CTLA-4 blocking induce sustained responses, only in a limited number patients. combination these diametric approaches may further improve survival, pre-clinical data concerning this approach is limited. We investigated, using...
<h3>Background</h3> T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of inhibitors as standalone therapies, impact inhibition on activity remains incompletely understood. Here we sought to characterize combined anti-CTLA-4 mAb (anti-CTLA-4) therapy, examining both T-cells tumor microenvironment (TME). <h3>Methods</h3> In mice, inhibition, via selumetinib, immune responses keyhole limpet...
Importance Nonclinical studies suggest that the combination of poly(ADP-ribose) polymerase and programmed cell death 1/programmed death–ligand 1 inhibitors has enhanced antitumor activity; however, patient populations may benefit from this have not been identified. Objective To evaluate whether avelumab talazoparib is effective in patients with pathogenic BRCA1/2 or ATM alterations, regardless tumor type. Design, Setting, Participants In pan-cancer tumor-agnostic phase 2b nonrandomized...
Abstract Background: Patients with HR− advanced/metastatic breast cancer (a/mBC) a low level of HER2 (immunohistochemistry [IHC] score 1+ or IHC 2+ and negative in situ hybridization [ISH]) have poor prognosis. Combining 1L chemotherapy immune checkpoint inhibitors can modestly improve outcomes vs alone, but treatment benefit is largely seen patients PD-L1+ disease. BEGONIA (NCT03742102) an ongoing 2-part, open-label platform study, evaluating safety efficacy D, anti–PD-L1 antibody, combined...
The primary analysis (median follow-up 34.9 mo across all arms) of the phase 3 POSEIDON study revealed a statistically significant overall survival (OS) improvement with first-line tremelimumab plus durvalumab and chemotherapy (T+D+CT) versus CT in patients EGFR ALK wild-type metastatic NSCLC (mNSCLC). D+CT had trend for OS that did not reach statistical significance. This article reports prespecified analyses after long-term >5 y). A total 1013 were randomized (1:1:1) to T+D+CT, D+CT, or...