Preclinical to clinical translation of anti-PD-1 blockade
نویسندگان
چکیده
Background Pembrolizumab (MK-3475), a humanized monoclonal IgG4 antibody against programmed death receptor 1 (PD-1), is currently being studied in clinical trials across more than 30 types of cancers. Immunotherapy with anti–PD-1 monoclonal antibodies such as pembrolizumab shows robust, durable anti-tumor activity in multiple indications including patients with advanced melanoma. A more complete understanding of the mechanism of action and biology associated with both response and resistance to pembrolizumab is critical to better inform on future clinical development and will also provide insight into the development of additional immuno-oncology therapies.
منابع مشابه
Immunogenic chemotherapy sensitizes non-small cell lung cancer to immune checkpoint blockade therapy in preclinical models
Background: Lung cancer is the top common cancer and cause of cancer-related death worldwide. Checkpoint blockade immunotherapies have shown extraordinarily anti-tumor effects, but only benefit the minority of patients whose tumors are pre-infiltrated by CD8+ T cells. However, the majority of solid tumors, including lung cancer are not immunogenic and CD8+ T cell infiltration is inconspicuous. ...
متن کاملSequential tumor and dual immune targeted immunotherapy: anti-lymphoma activity of Rituximab with 4-1bb stimulation and PD-1 blockade
To select maximally-efficacious, minimally-toxic regimens of combination tumorand immune-targeted therapy, preclinical testing in immune-competent models is required. We previously demonstrated 4-1bb(CD137) stimulation augmented the innate immune response mediated by CD137activated natural killers (NK) cells and the subsequent CD8 T cell adaptive immune response when administered after tumor-ta...
متن کاملCancer Therapy: Preclinical TargetingCD73Enhances theAntitumorActivity of Anti-PD-1 and Anti-CTLA-4 mAbs
Purpose: Monoclonal antibodies (mAb) that block programmed death (PD)-1 or cytotoxic T lymphocyte antigen (CTLA-4) receptors have been associated with durable clinical responses against a variety of cancer types and hold great potential as novel cancer therapeutics. Recent evidence suggest that targeted blockade of multiple immunosuppressive pathways can induce synergistic antitumor
متن کاملImmunogenic Chemotherapy Sensitizes Renal Cancer to Immune Checkpoint Blockade Therapy in Preclinical Models
BACKGROUND Renal cell carcinoma (RCC) is among the most common malignant cancers of males worldwide. For advanced RCC patients, there still is no effective therapy. Immune checkpoint blockade therapies have shown benefits for many cancers, but previous clinical trials of immune checkpoint blockade therapies in RCC patients achieved only modest results. MATERIAL AND METHODS We explored the effec...
متن کاملImproved anti-tumor immunity and efficacy upon combination of the IDO1 inhibitor GDC-0919 with anti-PD-l1 blockade versus anti-PD-l1 alone in preclinical tumor models
Improved anti-tumor immunity and efficacy upon combination of the IDO1 inhibitor GDC-0919 with anti-PD-l1 blockade versus anti-PD-l1 alone in preclinical tumor models Jessica Spahn, Jing Peng, Edward Lorenzana, David Kan, Thomas Hunsaker, Ehud Segal, Mario Mautino, Erik Brincks, Andrea Pirzkall, Sean Kelley, Sami Mahrus, Liling Liu, Stephanie Dale, Cristine Quiason, Elizabeth Jones, Yichin Liu,...
متن کامل