Multimodal imaging of immune cell therapies against cancer
Abstract/Contents
- Abstract
- Immunotherapies focus on reprogramming a patient's immune system to better recognize and target tumor cells. In particular, T-cells can be engineered ex vivo to either target a specific tumor antigen (via a chimeric antigen receptor) or a diverse tumor antigen repertoire (via a dendritic cell vaccine). As novel adoptive T-cell strategies progress through preclinical development and clinical trials, the ability to accurately monitor therapeutic response becomes of even greater need. Molecular imaging allows for real-time insight of the local and systemic patient response to immunotherapies, providing more dynamic information than anatomic tumor volume alone. Here I will discuss molecular imaging strategies for the in vivo monitoring and visualization of immunotherapies and their impact to elucidate the therapeutic efficacy of clinically-relevant adoptive T-cell therapies. First, I will discuss the PET reporter gene imaging and drug-induced ablation of chimeric antigen receptor (CAR) T-cells in solid tumors through the HSV1-sr39tk gene. This dual-function system can provide insight into systemic CAR T-cell migration and proliferation during clinical trials while serving as a suicide switch to limit potential toxicities. Secondly, I will present the first longitudinal fluorescence-based intravital microscopy imaging of CAR T-cells within an orthotopic glioblastoma preclinical model to illustrate the necessity of radiation therapy for complete therapeutic response. This preclinical imaging technique can help us understand immune cell dynamics within the tumor microenvironment with a high-level of spatial and temporal resolution. Third, I will utilize intravital imaging to understand the potential for dendritic cell vaccines in the treatment of glioblastoma. These strategies highlight the potential of molecular imaging both to lend insight on fundamental adoptive T-cell biology and to translate these therapies into the clinic.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Murty, Surya |
|---|---|
| Degree supervisor | Gambhir, Sanjiv Sam |
| Thesis advisor | Gambhir, Sanjiv Sam |
| Thesis advisor | Fordyce, Polly |
| Thesis advisor | James, Michelle (Michelle Louise) |
| Degree committee member | Fordyce, Polly |
| Degree committee member | James, Michelle (Michelle Louise) |
| Associated with | Stanford University, Department of Bioengineering. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Surya Murty. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Surya Murty
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