# NIH grant: Engineering Immunostimulatory Spherical Nucleic Acids for B cell adoptive therapy (1R01CA303489-01A1) — retained record

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[original source ↗](https://reporter.nih.gov/project-details/1R01CA303489-01A1)

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NIH grant 1R01CA303489-01A1: Engineering Immunostimulatory Spherical Nucleic Acids for B cell adoptive therapy
Institute: {'code': 'CA', 'abbreviation': 'NCI', 'name': 'National Cancer Institute', 'admin_org_id': '12500008', 'admin_funding_url': ''}. PI: CHAD A. MIRKIN. Award: $660525.
Start: 2026-08-01T00:00:00.
Prostate cancer (PCa) remains one of the leading causes of cancer-related death in men, highlighting the need
for innovative therapies. Although immune checkpoint blockade (ICB) has been approved for the treatment of a
range of malignancies, multiple clinical trials with ICB therapies have not met their endpoints in patients with
metastatic castration resistant prostate cancer (mCRPC). Aside from ICB with tissue agnostic indications,
sipuleucel-T (Provenge™), an activated cellular product, is the only immunotherapy approved by the FDA for
mCRPC. However, objective responses are generally not observed with its use, reducing enthusiasm for it in the
clinic. Immune-activated, and antibody (Ab)-producing B cells enriched in localized prostate cancer have been
shown to be associated with improved outcomes, emphasizing the importance of further trials utilizing B cells in
reviving PCa immunotherapy.
The current proposal has devised a novel strategy to sensitize an immunologically “cold” prostate tumor to
ICB by adoptive cell therapy (ACT) using peripheral B cells trained ex vivo with IS-SNA nanostructures (B-cellSNA)
that present TLR9 agonist CpG oligonucleotides at the surface together with prostate cancer-specific antigens
(PCa Ags, e.g. PAP and PSMA). Although DCs (as in sipuleucel-T) and T cells present advantages for ACT in
terms of cytotoxicity and ex vivo proliferation capacity, the unique structural properties of IS-SNA enable their
efficient entry into B cells for optimal activation ex vivo easily for clinical use. Preclinical research has
demonstrated that systemic adminsrtation of B-cellSNA is a superior treatment for PCa compared to relative DC
vaccines or local IS-SNA vaccines. We hypothesize that ACT using PCa Ag-B-cellSNA will induce potent and
durable antitumor antigen-specific CD8+ T cell immunity concomitant with enhanced humoral immunity against
mCRPC especially when combined with ICB. These studies introduce a new approach for activating peripheral
B cells ex vivo with specialized nanoparticles carrying immune adjuvants that may be more suitable to treat
advanced PCa, and other immunologically “cold” malignancies refractory to ICB.
Immunocompetent C57BL/6J and FVB mouse tumor models are selected to enable rigorous analysis of
cancer progression and antitumor immune responses within an intact, physiologically relevant immune system,
complementary to the proposed humanized tumor models and human specimen studies. These well..established
syngeneic models, together with available genetic tools, are essential for dissecting tumor–immune interactions
that cannot be fully captured by alternative in vivo or ex vivo model systems.
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