Development and characterization of immunogenic genetically engineered mouse models of pancreatic cancer

Insights into mechanisms of immune escape have fueled the clinical success of immunotherapy in many cancers. However, pancreatic cancer has remained largely refractory to checkpoint immunotherapy. To uncover mechanisms of immune escape, we have characterized two preclinical models of immunogenic pancreatic ductal adenocarcinoma (PDAC). In order to dissect the endogenous antigen-specific T cell response in PDAC, lentivirus encoding the Cre recombinase and a tumor specific antigen (SIINFEKL, OVA[subscript 257-264]) was delivered to Kras[superscript LSL-G12D/+]; Trp[superscript 53flox/flox] (KP) mice. We demonstrate that KP tumors show distinct antigenic outcomes: a subset of PDAC tumors undergoes clearance or editing by a robust antigen-specific CD8+ T cell response, while a fraction undergo immune escape. Subsequently, we have developed an immunogenic pancreatic tumor organoid orthotopic transplant model.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2020

Author dc:creator

• Lambert, Laurens J.(Laurens Johannes)

Advisor dc:contributor.advisor

• Tyler Jacks.

• Biology.

Statement dc:rights

• MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/129020

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/129020