658 KAN-001, a defined live biotherapeutic product (LBP) for NSCLC, enhances ICI response in preclinical models and demonstrates manufacturing consistency and strain-resolved viability
Notice bibliographique
Résumé
Background The gut microbiome modulates host immunity and responses to immune checkpoint inhibitors (ICIs) in cancers such as non-small cell lung cancer (NSCLC). Fecal microbiota transplantation (FMT) from ICI-responsive donors can improve outcomes in ICI-refractory patients, but FMT-based approaches suffer from donor availability, compositional variability, safety issues, and limited scalability. KAN-001 is a fully defined, Live Biotherapeutic Product (LBP) comprised of dozens of strains and designed to recapitulate the beneficial properties of responder FMT while offering a consistent and scalable manufacturing process supported by strain-level assays. Importantly, the strains comprising the product were isolated from a cancer patient who obtained a complete response to PD-1 therapy, and whose FMT was able to elicit response in cancer patients with tumors initially refractory to ICI. We report preclinical efficacy, strain engraftment data, and process development highlights supporting the planned clinical evaluation of KAN-001.Methods KAN-001 candidates were evaluated in the MCA205 murine tumor model in combination with anti-PD-1 therapy. Comparative arms included treatment with FMT from ICI-non-responder donors. Engraftment of KAN-001 strains was assessed in vivo by metagenomic sequencing and HiPR-FISH, a high-plex imaging approach that enables spatial mapping of strain colonization in host tissue. The use of the HiPR-FISH platform also enabled the optimization of KAN-001 candidates, including strain additions through HiPR-ID-based targeted isolation. Run-to-run manufacturing consistency was assessed using small-scale production runs analyzed by metagenomics and HiPR-Vie, a HiPR-FISH-based platform allowing strain-level viability profiling of complex microbial communities.Results KAN-001 combined with ICI treatment resulted in tumor volume regression superior to FMT from ICI-non-responder donors, with optimized candidates leveraging HiPR-FISH showing improved tumor control in the murine model. Metagenomic profiling confirmed reproducible in vivo engraftment of KAN-001 strains, with HiPR-FISH revealing spatially distinct colonization patterns across the GI tract. Manufacturing process development runs demonstrated consistent strain abundance across replicates, and HiPR-Vie analysis confirmed viable representation of all strains across runs.Conclusions KAN-001 is a rationally designed, defined LBP that enhances ICI response in multiple preclinical mouse models and exhibits robust manufacturing and analytical tractability. A Phase 1 clinical trial is planned in NSCLC patients with both ICI naïve and refractory cohorts. Primary endpoints will include safety and tolerability, with secondary assessments of engraftment and preliminary efficacy. KAN-001 will be administered orally in an encapsulated frozen liquid formulation with induction and maintenance dosing. Microbiome profiling will be performed throughout the trial to characterize host-microbiome interactions and identify potential response biomarkers.Acknowledgements We thank Nadim Ajami and Jennifer Wargo of the MD Anderson Cancer Center for their continued support of the KAN-001 program.Ethics Approval The in vivo mouse study was approved by the Institutional Animal Care Committee (CIPA) and carried out in compliance with the Canadian Council at the CRCHUM.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».