# Tumor-directed immunostimulatory nanoparticles for novel 'prime-pull'cancer vaccination > **NIH NIH K22** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2022 · $194,308 ## Abstract PROJECT SUMMARY Despite their transformative promise, traditional cancer vaccines have had poor clinical responses since vaccine-specific systemic T cells often cannot traffic to immunosuppressed “cold” tumors. Traditional vaccines generate only a lymph node-derived augmentation or “prime” of systemic CD8+ T cells that are trained to comprehensively seek and eliminate specific target tumor cells. Traditional strategies, however, have been short-sighted in that they have failed to develop methods to recruit these T cells to the “cold” tumor microenvironment (TME) that advances by building a formidable local immunosuppressive barrier driven largely by dysfunctional innate immune cells. Our strategy seeks to reprogram dysfunctional tumor-resident innate antigen-presenting cells (APCs), such as dendritic cells (DCs) and macrophages, by driving a local anti- tumor immune response with a proinflammatory cytokine gradient that reshapes the TME from non-inflamed and “cold” to inflamed and “hot” to recruit or “pull” systemic T cells in from a “prime”. In our recent Cancer Research paper (Atukorale et al. 2019) and additional preliminary data, we report on the development of a “pull” strategy based on a novel immunostimulatory nanoparticle (immuno-NP) that is significant due to key engineering design features. Immuno-NPs co-encapsulate two synergistic immune agonists on the same particle, cdGMP, an agonist of the STING pathway, and MPLA, an agonist of the TLR4 pathway, to promote a robust production of proinflammatory Type I interferon ß in target APCs. Immuno-NPs can be safely delivered in the systemic blood circulation to achieve widespread and preferential deposition in the tumor perivascular regions that are rich in their target APCs. Immuno-NPs drive a powerful local self-amplifying anti-tumor immune response that harnesses otherwise “exhausted” immunosuppressed local CD8+ T cells as the key effectors of tumor clearance, which suggests highly effective “cold-to-hot” TME reprogramming. Our central hypothesis is that precise coupling of a standard lymph node-directed CD8+ T cell vaccine “prime” with a tumor-directed immuno-NP “pull” for a novel “prime-pull” approach can provide the key missing link for effective cancer vaccination. Specific Aim 1 will identify optimal function of an immuno-NP pull in terms of immuno-NP design and co-treatment with anti-PD1. Specific Aim 2 will develop a precise “prime-pull” coupling schedule. Specific Aim 3 will evaluate safety and toxicity for effective dose/scheduling “prime-pull” regimens. Dr. Atukorale's career goals are to establish a nanomaterials-based cancer immuno-engineering laboratory as an independent investigator. She will develop immuno-nanomaterials tools that drive, quantify, and interrogate immunity, specifically in the context of lethal cancers. Dr. Atukorale's strong career development plan includes significant new research collaborations, a senior advisory committee, research presentations, faculty-l... ## Key facts - **NIH application ID:** 10470310 - **Project number:** 5K22CA262355-02 - **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST - **Principal Investigator:** Prabhani Atukorale - **Activity code:** K22 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2022 - **Award amount:** $194,308 - **Award type:** 5 - **Project period:** 2021-09-01 → 2024-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10470310 ## Citation > US National Institutes of Health, RePORTER application 10470310, Tumor-directed immunostimulatory nanoparticles for novel 'prime-pull'cancer vaccination (5K22CA262355-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10470310. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*