- Enhanced anti-tumor activity, improved overall survival, and an exponential increase in CAR-T cell proliferation was observed with GM-CSF neutralization
- Lenzilumab (an anti-GM-CSF antibody) used in combination with CAR-T significantly reduces neuro-inflammation, prevents cytokine release syndrome and improves durable control of leukemic disease
- GM-CSF neutralization with lenzilumab is a next generation strategy to improve efficacy, safety and durability of CAR-T
BURLINGAME, Calif., Feb. 15, 2019 (GLOBE NEWSWIRE) -- Humanigen, Inc., (HGEN) (“Humanigen”) announced today that the editors of ‘blood’® , which is widely regarded as a premier journal in hematology and the official journal of the American Society of Hematology, selected their study entitled “GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts” and a key image from the associated manuscript for the front cover of the current edition of the journal. The study was conducted using lenzilumab, the company’s proprietary Humaneered® anti-GM-CSF monoclonal antibody, and the manuscript is available, along with the front cover image, at http://www.bloodjournal.org/content/133/7/697
The study was designed to closely replicate the effects seen in CAR-T clinical trials and utilized human acute lymphoblastic leukemia (ALL) cells, human CD19 targeted CAR-T (CART19) cells, and human peripheral blood mononuclear cells (PBMCs) and conducted in mice. Within 4-6 days after treatment with CART19, animals developed a syndrome which recapitulated signs consistent with neuro-inflammation (NI) and cytokine release syndrome (CRS). NI was measured by brain magnetic resonance imaging (MRI) analyses, revealing abnormal T1 hyperintensities indicative of neuro-inflammation, blood-brain-barrier disruption and possibly brain edema. This syndrome is associated with elevation of key serum cytokines and chemokines 4-11 days post-CART19 injection, similar to human CRS.
The prophylactic administration of lenzilumab with CART19 therapy resulted in significant improvement in leukemic disease control sustained for at least 35 days post-CART19 administration, compared to CART19 plus isotype control. Other significant findings included increased CART19 cell proliferation, enhanced anti-tumor activity, and improved overall survival with GM-CSF neutralization.
In addition to improved efficacy, lenzilumab in combination with CART19 therapy prevented CRS and resulted in a 75% reduction in NI by quantitative MRI.
“It is noteworthy to see that ‘blood’ selected the Humanigen study and its key image as the front cover visual. This selection was from many other manuscripts that could have been chosen for this edition which comes shortly after the ASH annual meeting,” commented Dr. Cameron Durrant, chief executive officer of Humanigen. “This work represents a significant advance in understanding how to improve efficacy and safety of CAR-T. Our results strongly suggest that modulating myeloid cells through GM-CSF neutralization may help improve the durability of response to CAR-T and prevent or eliminate toxicities.”
About Humanigen, Inc.
Humanigen, Inc. is developing its portfolio of Humaneered® monoclonal antibodies to address cutting-edge CAR-T optimization and oncology treatments advancing safer, better, and more effective cancer therapies. Derived from the company’s Humaneered® platform, lenzilumab and ifabotuzumab are monoclonal antibodies with first-in-class mechanisms. Lenzilumab, which targets GM-CSF, is in development as a potential biologic therapy to make CAR-T therapy safer and more effective, as well as a potential treatment for hematologic cancers. Ifabotuzumab, which targets the Eph type-A receptor 3 (EphA3), is being explored as a potential treatment for glioblastoma multiforme (GBM) and other solid tumors, both as naked antibody and as part of an antibody-drug conjugate, as well as a backbone for a novel CAR-T construct, and a bispecific antibody platform. For more information visit www.humanigen.com
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