Pipeline / 03 · Neuro & Oncology

GBM Immunotherapy Program

An immune-based therapeutic approach to glioblastoma — engineered to cross the blood-brain barrier and activate anti-tumor response in the CNS.

TARGET DISEASE ANALYSIS Glioblastoma — two barriers, one solution. BARRIER 01 The Blood-Brain Barrier 98% of small molecules — and nearly 100% of biologics — fail to cross. MACRO HRD APPROACH → AH-D peptide BBB facilitation → RVG29-targeted LNP delivery → MK16-BLNP for CNS access BARRIER 02 The Suppressive TME Glioblastoma actively disarms infiltrating immune cells. MACRO HRD APPROACH → TCGA IS1–IS4 stratification → Multi-epitope mRNA vaccine → CRISPR PD-1/TIM-3 KO
Target disease analysis for glioblastoma — defining tumor immunoarchitecture (immune-cold vs immune-hot TCGA IS1–IS4 subtypes), BBB permeability profiles by delivery route, and tumor exosome dynamics enabling AH-D countermeasure design.
Premise

The problem we are solving.

Glioblastoma is the most lethal primary brain tumor, with median survival under 15 months despite maximal surgery, radiation, and chemotherapy. Two challenges have resisted solution: the blood-brain barrier prevents most therapies from reaching the tumor, and the glioblastoma microenvironment is profoundly immunosuppressive, disarming whatever does arrive.

MACRO HRD's GBM program addresses both. AH-D peptide engineering facilitates BBB penetration. Multi-epitope mRNA constructs encode neoantigens alongside pan-MHC anchor domains to drive durable T-cell response. Engineered γδ and CD8+ T cells armored against the suppressive tumor microenvironment deliver the cytotoxic payload.

Approach

How we tackle it.

The program integrates four modalities: BBB-facilitating peptides, mRNA neoantigen vaccines with brain-targeted delivery, tri-specific antibody bridges, and engineered γδ and CD8+ T cells armored to persist in the suppressive tumor environment.

GEDM-3DQ coordinates the sequence — timing vaccine priming, antibody recruitment, and cell-infusion windows — while continuously monitoring safety signals such as cytokine-release risk. The strategy is not one mechanism deployed harder; it is four mechanisms deployed correctly together.

FUNCTIONAL PAYLOAD DESIGN Multi-epitope mRNA construct, codon-optimized. 5' CAP 1-methylpseudo- uridine modified AH-D BBB facilitation 27-mer peptide NEOANTIGEN 1 Tumor-specific epitope #1 NEOANTIGEN 2 Tumor-specific epitope #2 NEOANTIGEN 3 Tumor-specific epitope #3 ANCHOR Pan-MHC binding domain 3' UTR Stability optimization 5′ to 3′ mRNA construct architecture Delivered via lipid nanoparticle (RVG29-targeted) or exosome (MK16-BLNP optimized for BBB).
Functional payload design for GBM — AH-D 27-mer peptide encoded for exosome disruption and BBB facilitation, multi-epitope construct with pan-MHC anchor domains, and codon-optimized mRNA with 1-methylpseudouridine and 5' cap.
Capabilities

What makes this real.

01
BBB penetration
AH-D peptide and RVG29-targeted delivery vehicles designed specifically for central nervous system access.
02
Multi-epitope neoantigen design
mRNA constructs encoding tumor-specific neoantigens with pan-MHC anchor domains for durable response across HLA types.
03
Armored T cell platforms
CRISPR-edited PD-1/TIM-3 deletion with IL-15/IL-21 cytokine support to resist the immunosuppressive tumor microenvironment.
04
Coordinated four-modality sequencing
GEDM-3DQ coordinates peptide, vaccine, antibody, and cell therapy timing for maximal synergy.
Clinical & Research Network

Built with established partners.

The glioblastoma program is advanced through a multi-institutional consortium spanning leading academic medical centers, neuro-oncology surgical hubs, and population-immunogenetics expertise — ensuring the therapeutic design is validated across diverse patient populations rather than a single cohort.

The engineered cell platform is supplied by a NASDAQ-listed, clinical-stage γδ T-cell partner with an active first-in-human trial — bringing GMP manufacturing capacity and an off-the-shelf, donor-derived cell source to the collaboration. MACRO HRD contributes the AI decision layer that guides design and monitors safety across the program.

Where It Connects

Part of an integrated platform.

01 · Platforms
Functional Peptide Platform
A library of 20,000+ engineered peptides for membrane penetration, targeted delivery, and biological modulation.
01 · Platforms
Engineered Immune Cells Platform
CAR-like NK systems and γδ T cell therapies for adaptive, MHC-independent elimination of diseased cells.
03 · Neuro & Oncology
Brain Mapping Platform
AI-assisted neuro-biomarker discovery through integrated proteomics and genomics at Beijing Tiantan Hospital.
01 · Platforms
GEDM-3DQ Decision Engine
Gradient Equilibrium Decision Modeling in 3-Dimensional Quadrant — the AI spine of every MACRO HRD program.
⸻ Continue the platform

“The tumor has four defenses. We bring four answers — timed to arrive together.”

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