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Combination therapy for mCRPC with immune checkpoint inhibitors, ADT and vaccine: A mathematical model
- Source :
- PLoS ONE, Vol 17, Iss 1, p e0262453 (2022), PLoS ONE, Vol 17, Iss 1 (2022), PLoS ONE
- Publication Year :
- 2022
- Publisher :
- Public Library of Science (PLoS), 2022.
-
Abstract
- Metastatic castration resistant prostate cancer (mCRPC) is commonly treated by androgen deprivation therapy (ADT) in combination with chemotherapy. Immune therapy by checkpoint inhibitors, has become a powerful new tool in the treatment of melanoma and lung cancer, and it is currently being used in clinical trials in other cancers, including mCRPC. However, so far, clinical trials with PD-1 and CTLA-4 inhibitors have been disappointing. In the present paper we develop a mathematical model to assess the efficacy of any combination of ADT with cancer vaccine, PD-1 inhibitor, and CTLA-4 inhibitor. The model is represented by a system of partial differential equations (PDEs) for cells, cytokines and drugs whose density/concentration evolves in time within the tumor. Efficacy of treatment is determined by the reduction in tumor volume at the endpoint of treatment. In mice experiments with ADT and various combinations of PD-1 and CTLA-4 inhibitors, tumor volume at day 30 was always larger than the initial tumor. Our model, however, shows that we can decrease tumor volume with large enough dose; for example, with 10 fold increase in the dose of anti-PD-1, initial tumor volume will decrease by 60%. Although the treatment with ADT in combination with PD-1 inhibitor or CTLA-4 inhibitor has been disappointing in clinical trials, our simulations suggest that, disregarding negative effects, combinations of ADT with checkpoint inhibitors can be effective in reducing tumor volume if larger doses are used. This points to the need for determining the optimal combination and amounts of dose for individual patients.
- Subjects :
- Male
Urology
Immune Cells
Science
Immunology
Cancer Treatment
Antigen-Presenting Cells
Cytotoxic T cells
Biochemistry
Cancer Vaccines
Lung and Intrathoracic Tumors
White Blood Cells
Animal Cells
Medicine and Health Sciences
Humans
Immune Checkpoint Inhibitors
Blood Cells
Multidisciplinary
T Cells
Prostate Cancer
Prostate Diseases
Cancers and Neoplasms
Biology and Life Sciences
Androgen Antagonists
Cell Biology
Dendritic Cells
Models, Theoretical
Hormones
Genitourinary Tract Tumors
Prostatic Neoplasms, Castration-Resistant
Oncology
Androgens
Medicine
Drug Therapy, Combination
Immunotherapy
Cellular Types
Research Article
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....430d4fd99bc63158129c5126151acd39