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Xiang Yan
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P3.07 - Immunology and Immunotherapy (ID 723)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.07-001 - Overcoming Resistance to Anti-PD Immunotherapy in a Syngeneic Mouse Lung Cancer Model Using Adenovirus-Mediated Gene Therapy (ID 7505)
09:30 - 09:30 | Presenting Author(s): Xiang Yan
- Abstract
Background:
Anti-PD immunotherapy has provided a new therapeutic opportunity for lung cancer. However, overall objective response rates are relatively low in all NSCLC patients who receive anti-PD therapy. We hypothesized that the barrier to the success of anti-PD therapy in most NSCLC patients can be overcome by stimulating the inflammatory response at cancer sites through adenovirus-mediated gene therapy.
Method:
We determined combination effects of anti-PD immunotherapy and oncolytic adenoviral vector-mediated tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) gene therapy (Ad/E1-TRAIL) or adenoviral-mediated TP53 (Ad/CMV-TP53) gene therapy in syngeneic mice bearing subcutaneous tumors derived from M109 lung cancer cells.
Result:
Both anti–PD-1 and anti–PD-L1 antibodies failed to elicit obvious therapeutic effects in the M109 tumors. Intratumoral administration of Ad/E1-TRAIL or Ad/CMV-TP53 alone suppressed tumor growth in animals preexposed to an adenovector and bearing subcutaneous tumors derived from M109 cells. However, combining either anti–PD-1 or anti–PD-L1 antibody with these two adenoviral vectors elicited the strongest anticancer activity in mice preexposed to adenoviral vectors. .Figure 1Figure 2
Conclusion:
Our results showed that the mouse lung adenocarcinoma M109 cell line is resistant to anti–PD-1 and anti–PD-L1 antibody treatment, and this resistance can be overcome by adenovirus-mediated gene therapy.
