The most common primary malignant brain tumors in adults are gliomas. Glioblastoma is the most prevalent and aggressive tumor subtype of glioma. Current standards for the treatment of glioblastoma include a combination of surgical, radiation, and drug therapy methods. The drug therapy currently includes temozolomide (TMZ), an alkylating agent, and bevacizumab, a recombinant monoclonal IgG1 antibody that selectively binds to and inhibits the biological activity of vascular endothelial growth factor. Supplementation of glioblastoma radiation therapy with TMZ increased patient survival from 12.1 to 14.6 months. The specificity of TMZ effect on brain tumors is largely determined by special aspects of its pharmacokinetics. TMZ is an orally bioavailable prodrug, which is well absorbed from the gastrointestinal tract and is converted to its active alkylating metabolite 5-(3-methyl triazen-1-yl)imidazole-4-carbozamide (MTIC) spontaneously in physiological condition that does not require hepatic involvement. MTIC produced in the plasma is not able to cross the BBB and is formed locally in the brain. A promising way to increase the effectiveness of TMZ chemotherapy for glioblastoma is to prevent its hydrolysis in peripheral tissues and thereby increase the drug concentration in the brain that nanoscale delivery systems can provide. The review discusses possible ways to increase the efficacy of TMZ using nanocarriers.

Purpose: SIRPα+ macrophages can mediate resistance to lenalidomide and rituximab in patients with B-cell non-Hodgkin lymphoma (B-NHL). Evorpacept (ALX148) is a novel CD47 blocker that abrogates interactions between lymphoma cells and SIRPα+ macrophages. Patients and Methods: Adult patients with B-NHL who had received at least two prior lines of systemic therapy were included in this single-arm phase I study (NCT05025800). Evorpacept was administered intravenously, in a 28-day cycle, until progression at two dose levels (DL): 30 mg/Kg on day (D) 1 and D15 (DL1) or 60 mg/Kg on day 1 (DL2); rituximab 375 mg/m2 i.v. was given weekly during cycle 1 and on D1 during cycles 2 to 6; and lenalidomide 20 mg was given orally from D1 to D21 during cycles 1 to 6. Single-cell RNA sequencing was performed on tumor biopsies collected before treatment and during cycle 1. Results: Twenty patients were included in this study. The median age was 61 (27–85) years, and 18 patients (90%) had indolent B-NHL. Three patients were treated at DL1, 17 at DL2, and no dose-limiting toxicity was observed. The most common grade 3 to 4 adverse events included neutropenia (60%), infections (30%), and alanine transferase increase (15%). Sixteen (80%) patients achieved complete response, and after a median follow-up of 28 months, 2-year progression-free survival rate was 69%. During treatment, a significant increase in T cells and macrophages was observed, and macrophage pathways associated with anti-tumoral activity were upregulated. Conclusions: Evorpacept plus lenalidomide and rituximab has a safe toxicity profile and promising anti-tumoral activity, and induces favorable biological effects on the tumoral immune microenvironment.

Associations between cytokine changes and progression

Laboratory trends during treatment

UMAP from single cell RNA sequencing

Eligibility criteria and DLT definition