CSF-1R-Dependent Lethal Hepatotoxicity When Agonistic CD40 Antibody Is Given before but Not after Chemotherapy
| Autor: | Katelyn T. Byrne, Robert H. Vonderheide, David L. Bajor, Nathan H. Leisenring |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Stromal cell Drug-Related Side Effects and Adverse Reactions medicine.medical_treatment T cell Immunology Receptor Macrophage Colony-Stimulating Factor Pharmacology Article 03 medical and health sciences Mice 0302 clinical medicine Clinical Protocols Drug Therapy Cell Line Tumor medicine Immunology and Allergy Animals Humans Drug Interactions CD40 Antigens Chemotherapy CD40 biology business.industry Cancer Antibodies Monoclonal Immunotherapy Neoplasms Experimental medicine.disease Immune checkpoint Carcinoma Ductal Mice Inbred C57BL Pancreatic Neoplasms 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis biology.protein Antibody business Genetic Engineering Liver Failure |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 197(1) |
| ISSN: | 1550-6606 |
| Popis: | Cancer immunotherapies are increasingly effective in the clinic, especially immune checkpoint blockade delivered to patients who have T cell–infiltrated tumors. Agonistic CD40 mAb promotes stromal degradation and, in combination with chemotherapy, drives T cell infiltration and de novo responses against tumors, rendering resistant tumors susceptible to current immunotherapies. Partnering anti-CD40 with different treatments is an attractive approach for the next phase of cancer immunotherapies, with a number of clinical trials using anti-CD40 combinations ongoing, but the optimal therapeutic regimens with anti-CD40 are not well understood. Pancreatic ductal adenocarcinoma (PDA) is classically resistant to immunotherapy and lacks baseline T cell infiltration. In this study, we used a tumor cell line derived from a genetically engineered mouse model of PDA to investigate alterations in the sequence of anti-CD40 and chemotherapy as an approach to enhance pharmacological delivery of chemotherapy. Unexpectedly, despite our previous studies showing anti-CD40 treatment after chemotherapy is safe in both mice and patients with PDA, we report in this article that anti-CD40 administration |
| Databáze: | OpenAIRE |
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