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Dynamic Targetable Extracellular Vesicle Surface Proteins Monitor Depth of Response to CAR T Therapy

Res Sq [Preprint]. 2026 Mar 18:rs.3.rs-8913641. doi: 10.21203/rs.3.rs-8913641/v1.

ABSTRACT

Extracellular vesicles (EVs) represent a promising liquid biopsy platform in multiple myeloma (MM). We developed an MM EV Surface Protein Assay to quantify and dynamically monitor four MM EV subpopulations defined by targetable MM surface proteins (BCMA, CD38, GPRC5D, and CD319) across 336 serial blood samples from 45 relapsed/refractory MM (RRMM) patients treated with anti-BCMA chimeric antigen receptor (CAR) T-cell therapy. All four MM EV subpopulations significantly decreased in 43 patients with initial response, while BCMA+, GPRC5D+, and CD319+ MM EVs increased in 19 patients with progression, and antigen escape was detected by BCMA+ MM EVs. MM EV subpopulations differentiated minimal residual disease (MRD) status and complemented MRD for detecting early relapse before clinical progression. Notably, CD319+ MM EVs were early predictors of progression-free and overall survival in MRD-negative patients. This assay enables noninvasive monitoring of deep response, progression, and antigen escape, and stratifies survival in MRD-negative patients with RRMM.

PMID:41890853 | PMC:PMC13015583 | DOI:10.21203/rs.3.rs-8913641/v1

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Beyond Pass-by-Pass Optimization: Intent-Driven IR Optimization with Large Language Models

arXiv:2602.18511v1 Announce Type: cross Abstract: Modern compilers optimize programs through a sequence of modular passes over intermediate representations (IR). While this pass-by-pass paradigm offers engineering benefits, it suffers from a pass coordination problem: locally beneficial transformations may block more profitable optimizations in later stages. This limitation stems from the lack of an explicit notion of optimization intent, defined as a holistic strategy for coordinating multiple transformations toward a global performance objective. Recent LLM-based approaches formulate IR optimization as an end-to-end generation task, thereby avoiding the traditional pass-by-pass structure. However, optimization intent remains implicit in these methods, forcing models to jointly infer optimization strategy and generate low-level transformations, which limits both correctness and performance. We propose IntOpt, the first intent-driven IR optimizer that explicitly separates high-level optimization intent from low-level analysis and transformation. IntOpt organizes IR optimization into three stages: intent formulation, intent refinement, and intent realization, enabling globally coordinated transformations. Experiments show that IntOpt achieves 90.5% verified correctness and 2.660x average speedup on 200-program test set, outperforming state-of-the-art LLM-based optimizers in both correctness and performance, and surpassing modern compiler with the -O3 option on 37 benchmarks with speedups of up to 272.60x.
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