The AMG 330 record is more coherently organized by an effector-context framework than by the conventional target-density-and-exposure paradigm. These findings indicate that endogenous-effector assays, paired target-effector biomarkers, and rational effector-support strategies are likely to be clinically informative complements to conventional cell-line potency and dose-escalation approaches in future CD33 TCE development.
P1/2, N=249, Active, not recruiting, Molecular Partners AG | Recruiting --> Active, not recruiting | Trial completion date: Dec 2029 --> May 2027 | Trial primary completion date: Dec 2027 --> May 2026
10 days ago
Enrollment closed • Trial completion date • Trial primary completion date • First-in-human
Cytotoxicity against TP53-deleted (DEL) primary AML cells and TP53-knockdown (KD) AML cell lines was reduced in co-cultures with T cells stimulated with the BiTE molecule AMG 330 (CD3×CD33)...RNA sequencing of T cells co-cultured with TP53 KD cells uncovered a transcriptional shift toward a senescent cell cycle profile. Our data collectively identify the immunosuppressive secretome of TP53-deficient AML as a key barrier to T-cell-engaging immunotherapies, underscoring an unmet clinical need for strategies able to restore T-cell function in TP53 KD AML.
TAC01-HER2 showed manageable toxicity and early efficacy for patients with HER2-positive gastric, GEJ or esophageal adenocarcinoma who have undergone extensive previous treatments. These results suggest that TAC may offer a promising approach to control T cell activity through cellular therapy.
However, intrinsic and acquired resistance to EGFR-targeted antibody therapies such as cetuximab remains a major limitation to achieving broad and durable treatment responses...Anti-tumor activity was additionally demonstrated in an EGFR-expressing CT-26 syngeneic tumor model in vivo. Collectively, these findings define a promising therapeutic strategy to overcome resistance to current EGFR-targeted therapies and provide a strong rationale for the development of next-generation T-cell - redirecting therapies in patients with EGFR-positive malignancies.
Immune checkpoint receptors (LAG3, CD27) connect via PPI intermediates to Ca2+ and K+ channels, targetable by relatlimab (FDA-approved) and varlilumab (Phase 2). This work maps previously unknown links between CRC driver genes and ion channel regulation, with the ataluren-RPS21-KCNQ2 axis ready for pharmacological testing.