blood-cancer

Engineering CAR-T cells to stay in bone marrow dramatically improves leukemia killing.

The bone marrow microenvironment protects leukemia cells from both chemotherapy and immunotherapy, inhibiting T cell infiltration. This study addressed this by engineering CD33-targeted CAR-T cells to express constitutively active Rac1 (Rac1V12)—a GTPase that controls cell migration and tissue…

Engineering CAR-T cells to stay in bone marrow dramatically improves leukemia killing.

Rac1V12-expressing CD33 CAR-T cells showed enhanced migration into bone marrow in vivo, maintained better immunological memory phenotype, and had lower tonic signaling—factors that improve T cell persistence and anti-tumor efficacy. In xenograft AML models, these cells achieved superior leukemia suppression and significantly prolonged survival.

Targeting the bone marrow niche resistance mechanism via Rac1 engineering represents a novel strategy for AML CAR-T therapy.

Key Findings

Active Rac1 (Rac1V12) enhanced T cell and CAR-T cell migration into bone marrow in vivo
Rac1V12 CD33 CAR-T cells showed superior anti-leukemia cytotoxicity in transwell killing assays
Xenograft models: Rac1V12 CAR-T cells robustly suppressed AML and extended survival
Engineered cells maintained better memory phenotype and lower tonic signaling
Rac1 engineering addresses bone marrow niche resistance to CAR-T therapy

Implications

Rac1 engineering could improve efficacy of CAR-T therapies in AML and potentially other hematological malignancies with bone marrow involvement. This addresses a fundamental barrier to cellular immunotherapy in leukemia.

Caveats

Preclinical study in cell lines and xenograft models; abstract-only. Human clinical validation needed. Safety of constitutively active Rac1 (which affects cytoskeletal dynamics broadly) requires extensive toxicology. Manufacturing complexity of engineered CAR-T cells is a translational challenge.

Source: FASEB journal : official publication of the Federation of American Societies for Experimental Biology — 2026-04-30

Landmark DCIS trial, CRC microbiome & AML combos

Two themes cut across this week’s 236 posts. The first is de-escalation: researchers are building rigorous evidence that patients can safely do less — skip lymph node surgery, forgo radiotherapy, watch pre-invasive lesions instead of cutting them out. The landmark result here is a randomized trial confirming that active surveillance

Colorectal Cancer Microbiome Discovery Platform

Analysis of 9,000+ patients revealed that only colorectal cancer — not other cancer types — consistently harbors distinct microbial communities, suggesting the gut microbiome has a unique relationship with colorectal carcinogenesis that could be exploited for diagnostics and treatment.

GBM Tumor Microenvironment Drug Target Atlas

Non-cancerous brain support cells were found to promote glioblastoma growth through paracrine signaling, and blocking this communication dramatically slowed tumor growth — revealing that GBM's microenvironment contains targetable vulnerabilities that are being systematically overlooked by drug…

BET Inhibitor Target Selectivity Database

BRD2 and BRD4 have fundamentally distinct functions — BRD2 prepares genes for activation while BRD4 triggers transcription — meaning that pan-BET inhibitors have been disrupting gene regulation in counterproductive ways, and the field now needs selective BRD4 inhibitors.

Engineering CAR-T cells to stay in bone marrow dramatically improves leukemia killing.

Key Findings

Implications

Caveats

Read more

Landmark DCIS trial, CRC microbiome & AML combos

Colorectal Cancer Microbiome Discovery Platform

GBM Tumor Microenvironment Drug Target Atlas

BET Inhibitor Target Selectivity Database