Tuesday, March 3, 2026 3/3/2026

Advancing treatment and understanding of immunotherapy in glioblastoma

Award Number: U19CA264338
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/10/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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Advancing treatment and understanding of immunotherapy in glioblastoma - SUMMARY/ABSTRACT Immunotherapy holds great promise for the treatment of glioblastoma; still, certain characteristics of glioblastoma present inherent therapeutic challenges. Herein, two experienced interdisciplinary laboratory and clinical teams at UCSFs Helen Diller Family Comprehensive Cancer Center and Northwestern University's Robert H. Lurie Comprehensive Cancer Center join efforts to develop innovative immunotherapy approaches against glioblastoma. This proposal leverages industry and institutional support to address three specific objectives: 1) to improve our understanding of the role of immunotherapy approaches in glioblastoma; 2) to improve our understanding of how to overcome the limitation the blood brain barrier and 3) to develop innovative immunotherapy treatments for glioblastoma, with associated early clinical trials focused on patients suffering from recurrent glioblastoma. Project 1, coordinated from Northwestern, will build on the team's preclinical results in mouse brain tumor models demonstrating an immunomodulatory and sensitization effect when immune checkpoint inhibitor therapy is preceded by a immunogenic dose of doxorubicin, an effect that can be further enhanced by ultrasound-based BBB opening. Support by innovative biotech companies (Agenus, AstraZeneca, Carthera) provide drugs or devices for preclinical and clinical investigation as well as specific expertise, assays and technology for investigations at both institutions, making this collaboration a very powerful consortium. The ensuing clinical trial will investigate the novel anti-PD1 checkpoint inhibitor balstilimab in conjunction with doxorubicin, with and without sonication for BBB opening. By administration of immune therapy prior to surgery (induction therapy, neoadjuvant treatment) the immune effect enables us to evaluate in vivo immune response in the resected brain tissue. We have previously identified pERk/MAPK activation as a biomarker for benefit from anti-PD1 treatment in recurrent glioblastoma; this and other markers will be explored furthermore. Four prospectively treated cohorts will be treated with and without induction therapy, and with and without BBB opening. Translational endpoints include immune response (tumor tissue, peripheral) and drug tissue concentration. Project 2, coordinated from UCSF, is a study based on the exciting novel synthetic Notch “synNotch” receptor CART system and pioneering T cell circuits that recognize tumor cells based on a “prime-and-kill” strategy. In this system, the first antigen, which is expressed exclusively on GBM cells (EGFRvIII), primes the T cells to induce expression of a CAR that recognizes IL-13Rα2 and EphA2, thereby eradicating GBM cells expressing either EphA2 or IL-13α2. Project 2's team hypothesizes that synNotch CART cells can revolutionize the CART therapy for glioblastoma by overcoming the challenges of off-tumor toxicity, antigen heterogeneity, and CART cell exhaustion. Thus, these synNotch-CART cells are hypothesized to be significantly more efficacious than conventional, constitutively expressed IL-13Rα2/EphA2 CART cells. Investigators will optimize the efficacy of the lead agent and test this hypothesis in the first in human clinical trial of this new class of agents in glioblastoma patients. This U19 proposal also has set aside funds for support of the distinctly important trans-GTN pilot projects, and for two cores (Administrative, Immune Monitoring & Biospecimen) that will support the efforts of the two projects. By addressing the overall specific objectives described, the research proposed in this U19 application has a high likelihood of changing the way immunotherapy is understood and utilized in glioblastoma. The innovative research described in this proposal will take advantage of the exceptional resources assembled by the well- established, collaborative group of clinical and basic scientists at UCSF and Northwestern.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Biology Research	001	5	2/10/2026	NON-COMPETING CONTINUATION	$0
2026	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Biology Research	000	5	12/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $838,812 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Biology Research	002	5	9/17/2025	NON-COMPETING CONTINUATION	$0
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Biology Research	001	5	8/12/2025	NON-COMPETING CONTINUATION	$838,812
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Biology Research	000	4	2/28/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $838,812

Issue Date FY: 2024 ( Subtotal = $796,871 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Biology Research	002	4	8/20/2024	NON-COMPETING CONTINUATION	$796,871
2024	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Biology Research	001	3	2/22/2024	NON-COMPETING CONTINUATION	$0
2024	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Biology Research	000	3	11/9/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $796,871

Issue Date FY: 2023 ( Subtotal = $821,970 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Biology Research	001	3	8/17/2023	NON-COMPETING CONTINUATION	$821,970
2023	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Biology Research	000	2	3/15/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $821,970

Issue Date FY: 2022 ( Subtotal = $821,968 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Biology Research	001	2	8/24/2022	NON-COMPETING CONTINUATION	$821,968
2022	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Biology Research	000	1	6/22/2022	NEW	$0
														Subtotal = $821,968

Issue Date FY: 2021 ( Subtotal = $885,236 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Biology Research	000	1	9/10/2021	NEW	$885,236
														Subtotal = $885,236

Grand Total All Awards = $4,164,857

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Advancing treatment and understanding of immunotherapy in glioblastoma

Award Number: U19CA264338

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/10/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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