Lung Cancer: Lung Cancer III |

Targeting Cancer Microenvironment Immunosuppression With High Affinity T-cell Activation Core (HATac) FREE TO VIEW

Chen Lin, BS; Yi Li, PhD
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State Key Laboratory of Respiratory Disease, Guangzhou, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A315. doi:10.1016/j.chest.2016.02.328
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SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: Herein we will determine the role of antigen presentation in the cancer cell death elicited by High Affinity T-cell activation core (HATac) fusion protein in the non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC) model, and study the signaling pathway affecting this process. Meanwhile, the relationship between HATac guided cytotoxcity and antigen spreading, or ICD, will also be investigated.

METHODS: 1. Identify cancer-testis (CT) antigen in NSCLC and TNBC 2. Produce HATac/ImmTAC and test whether antigen spreading can be induced through cross-presentation 3. Check if immunogenic cell death (ICD) can be induced by HATac/ImmTAC (detect calreticulin translocation, HMGB1 and ATP release) 4. Study the role of IFN-γin cross-presentation (detect Immunoproteasomes of tumor cells and DC) 5. Construct NOD. Cg-Prkdcscid Il2rgtm1Wjl Tg (HLA-A/H2-D/B2M) 1Dvs/SzJ NSCLC and TNBC animal model 6. Compare number and type of T cells in PBMC and tumor tissue during animal experiment

RESULTS: 1. Several CT antigens expressed in NSCLC (H1299) and TNBC (MDA-MB-231) 2.1G4 HATac/ImmTAC (NY-ESO-1 specific) has been produced and could redirect CD8+ T cell to kill tumor cells 3. Two elements (ATP and HMGB1) of ICD have been detected during cytotoxcity guided by HATac/ImmTAC

CONCLUSIONS: It is immensely important to test whether HATac can induce antigen spreading by cross-presentation, and to understand the fundamental mechanism underlying HATac guided cytotoxicity. And, ATP and HMGB1 release have been detected during the HATac/ImmTAC-redirected tumor cell killing, this provides an opportunity to find the right direction in the future.

CLINICAL IMPLICATIONS: This study will provide better rationales and evidence for the development of novel strategies to circumvent or overcome cancer immunosuppression.

DISCLOSURE: The following authors have nothing to disclose: Chen Lin, Yi Li

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