2022 World Conference on Lung Cancer (ePosters)-EP16.01-006. CD47 Inhibition Impairs the Growth of Orthotopic, Immune Competent Lung Tumour Models

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CD47 is an immunosuppressive protein that is overexpressed in lung and other cancers. In this study, researchers aimed to evaluate the impact of CD47 inhibition on lung tumor growth using two different murine lung tumor models. They used CRISPR/Cas9 technology to genetically inactivate CD47 in the tumor cells and verified the loss of CD47 expression using sequencing and flow cytometry. <br /><br />In vitro experiments showed that CD47 inactivation did not affect the growth of the tumor cells. However, in vivo competition assays revealed that tumor cells with CD47 loss-of-function were significantly underrepresented compared to wild-type cells in the tumors. Furthermore, mice bearing CD47 knockout tumors had significantly prolonged survival compared to those with wild-type tumors. Despite the growth disadvantage, the tumor cells with CD47 inactivation were not eradicated and were detected in tumors harvested at the endpoint of the competition assays. <br /><br />The results suggest that genetic inhibition of CD47 impairs the growth of lung tumors in these mouse models. This indicates that CD47 blockade could be an effective immunotherapeutic strategy for lung cancer, but the delivery of therapeutic antibodies to lung tumors needs to be optimized. The persistence of tumor cells with CD47 inactivation suggests that they may develop resistance to CD47 inhibition, and combination therapies may be necessary to maximize the effectiveness of CD47-targeted immunotherapy in clinical settings. <br /><br />The study highlights the importance of studying the interactions between immune and tumor cells in response to CD47-targeted therapy to improve therapeutic efficacy in patients. Further research could involve in vivo genetic screens to identify genes that sensitize lung tumors to CD47 inhibition.

Asset Subtitle

Kelsie Thu

Meta Tag

Speaker Kelsie Thu

Topic Tumour Biology and Biomarkers - Immune Biology & Immunotherapy

Keywords

CD47

lung cancer

murine lung tumor models

genetic inactivation

in vivo competition assays

survival

immunotherapeutic strategy

resistance

combination therapies

therapeutic efficacy