20P Tumor markers evolution in pts treated with TCE and association with radiologic response
Bibliographic record
Abstract
Background: The use of human B cells for antigen-and antibody discovery is on the rise due to the emergence of new techniques to tap into the human antigen-experienced B cell repertoire.To identify new targets for immunotherapy, we screened the B-cell repertoire of a patient with high-risk acute myeloid leukemia (AML) who mounted a potent graft versus leukemia immune response following allogeneic stem cell transplantation.Methods: KBA1413 is a fully human antibody identified using Kling's proprietary B cell screening platform, Kling-Select.KBA1413 derives from the B cells of an AML patient who remains in long term remission following allogeneic hematopoietic stem cell transplantation. Results:The antibody recognizes a unique, previously undescribed, sialylated epitope present on CD43 (CD43s).This epitope is expressed on across all AML subtypes and on myelodysplastic syndrome (MDS), as illustrated by KBA1413 reactivity to with freshly isolated blasts of over 60 randomly selected AML and MDS patients.In addition, KBA1413 also recognizes several solid tumor indications, including melanoma and breast cancer.KBA1413 triggers NK-mediated antibody dependent cell-mediated cytotoxicity (ADCC) against AML cells both in vitro and in vivo in human immune system mice xenografted with AML cells, suggesting that KBA1413 played a role in the graft versus leukemia response of the original donor patient. Conclusions:To increase its therapeutic potential KBA1413 was made into a bispecific T-cell engaging antibody (bTCE) that induced potent cytotoxicity in vitro and in vivo on cell lines and primary AML.Bifunctional targeting of AML with KBA1413 and a CD33 binder induced potent ADCC activitycytotoxicity in vitro, outperforming single agent activity.To increase the affinity of KBA1413, we further optimized binding of KBA1413 with employed the Kling-Evolve platform, this allows for the in vitro maturation of B cell clones against targets of interest.We are further exploring the therapeutic potential of KBA1413 with affinity matured variants produced with Kling-Evolve.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".