Abstract A74: CAR-T cells harboring camelid single domain antibody as targeting agent to CEACAM6 antigen in pancreatic cancer
Bibliographic record
Abstract
Abstract Carcinoembryonic Antigen Related Cell Adhesion Molecule 6 (CEACAM6) is overexpressed in many types of human cancers such as breast, pancreatic, colorectal, and non-small-cell lung adenocarcinoma, and is an independent predictor of overall survival and disease free survival. Targeting this molecule by antibodies has slowed tumor progression in certain animal models. 2A3 is a camelid single domain antibody isolated from a whole cancer cell immunized llama library. The antibody binds specifically to the CEACAM6 antigen with high affinity (5nM as measured by SPR) and inhibits the proliferation of CEACAM6-expressing cancer cells in vitro. In this study, Chimeric-Antigen Receptor (CAR) T cells were engineered to target human CEACAM6 antigen by transducing the 2A3 antibody sequence to generate a modified chimeric CD28 signaling domain fused to chimeric CD3-zeta. Transduction efficiency and expression of 2A3 antibody were verified by flow cytometry. Co-incubation of CEACAM6-specific CAR-T (CEACAM6-CAR-T) cells with the CEACAM6-expressing pancreatic cell line BxPC-3 resulted in augmented cytotoxicity and cytokines (IL-2 and IFN-γ) release, suggesting potential anti-cancer activity of the CAR-T cells. Data from real-time cell analysis showed a significant increase in BxPC-3 cell cytotoxicity by CEACAM6-CAR-T cells, as compared to native T cells. However, CEACAM6-CAR-T cells showed much lower cytotoxic activity on negative control cell lines. The efficacy of CEACAM6-CAR-T cells in xenograft model was examined in vivo. BxPC-3 cells were inoculated subcutaneously into the hind flank of CIEA NOG mice. Three groups of mice then received intravenous injection of either PBS, native T cells, or CEACAM6-CAR-T cells, respectively, at day 1, 8, and 15. The data demonstrated very high efficacy of CEACAM6-CAR-T cells against the pancreatic cancer xenograft. CEACAM6-CAR-T cells significantly decreased the growth of the BxPC-3 xenograft as compared to that of native T cells (p-value=0.00025) and PBS (p-value=7.91x106). No toxic effect was observed based on body weight measurement. The results strongly support that CEACAM6-CAR-T cells can be used as an effective immunotherapy agent against CEACAM6-expressing cancers, and that camelid single domain antibodies can be easily adopted for CAR-T type therapies. Citation Format: Wah Yau Wong, Jamshid Tanha, Lakshmi Krishnan, Baomin Tian, Praveen Kumar, Kim Gaspar, Steve Demas, Sven Rohmann, Heman Chao. CAR-T cells harboring camelid single domain antibody as targeting agent to CEACAM6 antigen in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr A74.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".