Tumor specific epitopes on Podocalyxin as a target for ADC and CAR T cell therapy
Bibliographic record
Abstract
Abstract Podocalyxin (Podxl) is a heavily glycosylated sialomucin type 1 membrane protein that has been shown to be involved in cell adhesion, migration, and polarity. Although Podxl is found on a variety of normal cell types, it is aberrantly expressed in acute myeloid leukemia (AML) blasts, and its presence in breast, colorectal and glial malignancies is correlated with poor clinical outcome. Using the human triple negative breast cancer line MDA-MB-231, we have demonstrated a functional role for Podxl in tumor growth and metastasis in xenografted mice, and have recently developed high affinity antibodies to a tumor-specific post-translational modification of Podxl. Preliminary IHC data suggests that this post-translational modification on Podxl may found in glioblastoma, melanoma, and female reproductive tract tumors, but not on matched normal tissue. Staining intensity in melanoma samples correlates with stage of disease and is strongest in tissues collected from metastatic lesions. Preliminary experiments indicate that expression of this glyco-epitope is increased in myeloid leukemia cells lines by co-culture with bone marrow stromal cells or hypoxia, suggesting that the tumor microenvironment may contribute to the observed reactivity. Our lead antibody, Podo447, binds this tumor-associated glycoform of Podxl with high affinity and induces cytotoxicity in various tumor cell lines as an antibody drug conjugate (ADC), and when expressed as a human IgG1 Fc chimera stimulates antibody dependent cellular cytotoxicity. With its exquisite specificity for malignant tissues, and the number of potential indications, Podo447 is an ideal targeting arm for an antibody drug conjugate or CAR-T enabled therapeutic.
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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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".