Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jul 25;144(4):457-461.
doi: 10.1182/blood.2024024168.

Glofitamab stimulates immune cell infiltration of CNS tumors and induces clinical responses in secondary CNS lymphoma

James K Godfrey  1 , Lei Gao  1 , Geoffrey Shouse  1 , Joo Y Song  2 , Stacy Pak  3 , Brian Lee  3 , Bihong T Chen  4 , Avyakta Kallam  1 , John H Baird  1 , Guido Marcucci  1 , Lucy Ghoda  5 , Stephanie Vauleon  6 , Alexey V Danilov  1 , Alex F Herrera  1 , Larry W Kwak  1 , Lihua E Budde  1
Affiliations

Glofitamab stimulates immune cell infiltration of CNS tumors and induces clinical responses in secondary CNS lymphoma

James K Godfrey et al. Blood. .

Abstract

Although CD20×CD3 bispecific antibodies are effective against systemic B-cell lymphomas, their efficacy in central nervous system (CNS) lymphoma is unknown. Here, we report the CD20×CD3 bispecific glofitamab penetrates the blood-brain barrier, stimulates immune-cell infiltration of CNS tumors, and induces clinical responses in patients with secondary CNS.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: J.K.G. receives research support from Merck, Janssen, and Secura Bio. L.E.B. receives research support from Merck, Amgen, Cellular Biomedicine Group, Inc, and AstraZeneca; and provides consultancy as part of advisory board for ADC Therapeutics, AstraZeneca, AbbVie, Nurix, Kite Pharma, Bristol Myers Squibb, Janssen, Regeneron, Genentech, and Roche. G.S. provides consultancy as part of an advisory board for AstraZeneca, BeiGene, and Kite Pharma; and serves on a speaker’s bureau for BeiGene and Kite Pharma. S.V. is an employee of Roche. The remaining authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Glofitamab penetrates the BBB and induces responses in patients with secondary CNS lymphoma. (A) Bar graph demonstrating the concentration of glofitamab in patient (Pt)–derived samples from the CSF and plasma. The relative proportion of glofitamab in the CSF compared with the plasma is listed as a percentage within the stacked bars for patients with synchronous CSF and plasma collections. (B) Induction of T-cell activation by the CSF of glofitamab-treated patient samples, as assessed by CD25 and CD69 upregulation. Peripheral blood T cells from a healthy donor were incubated for 24 hours with patient-derived CSF or buffer control solution in the presence of the CD20+ lymphoma cell line, Raji, at a 5:1 effector/target ratio. T cells incubated with glofitamab (0.1 μg/mL) and Raji served as a positive control. ∗∗∗P < .001. (C) T-cell cytotoxicity of CD20+ lymphoma cells induced by the CSF from glofitamab-treated patients. Peripheral blood T cells from a healthy donor were incubated for 24 hours with patient-derived CSF or buffer control solution in the presence of the CD20+ lymphoma cell line, Raji, at a 5:1 effector/target ratio. The extent of cytotoxicity was assessed by live/dead flow cytometric staining and was compared with conditions lacking T cells. Karpas-299, a CD20-negative lymphoma cell line, was used as a negative control. Raji incubated with T cells and glofitamab (0.1 μg/mL) served as a positive control. ∗∗∗P < .001. (D) Serial brain magnetic resonance imaging (MRI) scans from patient 1 with CNS lymphoma before (left panel), after 2 months (middle panel), and after 4 months (right panel) of glofitamab monotherapy. Imaging shows a near-complete response to treatment with a significant decrease in size and contrast enhancement within the CNS lesion (arrows) on T1-weighted postgadolinium contrast axial images. CxDx, cycle and day of glofitamab treatment; ns, not significant.
See this image and copyright information in PMC

References

    1. Sun LL, Ellerman D, Mathieu M, et al. Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies. Sci Transl Med. 2015;7(287):287ra70. - PubMed
    1. Engelberts PJ, Hiemstra IH, de Jong B, et al. DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing. EBioMedicine. 2020;52 - PMC - PubMed
    1. Bacac M, Colombetti S, Herter S, et al. CD20-TCB with obinutuzumab pretreatment as next-generation treatment of hematologic malignancies. Clin Cancer Res. 2018;24(19):4785–4797. - PubMed
    1. Falchi L, Vardhana SA, Salles GA. Bispecific antibodies for the treatment of B-cell lymphoma: promises, unknowns, and opportunities. Blood. 2023;141(5):467–480. - PMC - PubMed
    1. Budde LE, Sehn LH, Matasar M, et al. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol. 2022;23(8):1055–1065. - PubMed

Publication types