Reprogramming cancer into antigen presenting cells as a novel immunotherapy
Abstract/Contents
- Abstract
- Therapeutic cancer vaccination seeks to elicit activation of tumor-reactive T cells capable of recognizing tumor-associated antigens (TAAs) and eradicating malignant cells. Here, we present a cancer vaccination approach utilizing myeloid lineage reprogramming to directly convert cancer cells into tumor reprogrammed-APCs (TR-APCs). Using syngeneic murine leukemia models, we demonstrate that TR-APCs acquire both myeloid phenotype and function, process and present endogenous TAAs, and potently stimulate TAA-specific CD4+ and CD8+ T cells. In vivo TR-APC induction elicits clonal expansion of cancer-specific T cells, establishes cancer-specific immune memory, and ultimately promotes leukemia eradication. We further show that both hematologic cancers and solid tumors, including sarcomas and carcinomas, are amenable to myeloid-lineage reprogramming into TR-APCs. Finally, we demonstrate the clinical applicability of this approach by generating TR-APCs from primary clinical specimens and stimulating autologous patient-derived T cells. Thus, TR-APCs represent a cancer vaccination therapeutic strategy with broad implications for clinical immuno-oncology.
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 | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Linde, Miles Hamilton |
|---|---|
| Degree supervisor | Majeti, Ravindra, 1972- |
| Thesis advisor | Majeti, Ravindra, 1972- |
| Thesis advisor | Bendall, Sean, 1979- |
| Thesis advisor | Engleman, Edgar G |
| Thesis advisor | Levy, Ronald, 1941 December 6- |
| Degree committee member | Bendall, Sean, 1979- |
| Degree committee member | Engleman, Edgar G |
| Degree committee member | Levy, Ronald, 1941 December 6- |
| Associated with | Stanford University, Department of Immunology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Miles Hamilton Linde. |
|---|---|
| Note | Submitted to the Department of Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/hd601vf0379 |
Access conditions
- Copyright
- © 2022 by Miles Hamilton Linde
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