About

Prabhani Atukorale is an Assistant Professor in the Biomedical Engineering Department at UMass Amherst. Her research focuses on immunoengineering, immunotherapeutics, novel nanomaterials, tumor immunology, tumor microenvironment, and synthetic tumor niches. She is involved in advancing applied research and development efforts aimed at translational milestones, including cancer vaccinations with 'super adjuvant' nanoparticles through her project 'Super Vax.' Her work contributes to the development of innovative therapeutic strategies and nanomaterials in the field of biomedical engineering.

Research topics

• Cancer research
• Immunology
• Internal medicine
• Medicine
• Biology
• Chemistry

Selected publications

• Tumor Homing Nanoparticle Immunotherapy for Acute Clearance and Mitigation of T-cell Exhaustion in Humanized High-Risk Neuroblastoma

  Molecular Cancer Therapeutics · 2026-03-26

  articleOpen accessSenior author

  Effective treatments for high-risk neuroblastoma, a pediatric malignancy with dismal survival outcomes, demand strategies that remodel the "cold" immunosuppressive tumor microenvironment (TME) to "hot" and proinflammatory. In this study, we interrogate the mechanistic efficacy of a pathogen-inspired nanoparticle (NP) technology that leverages the advantages of lipids to co-deliver a combination of physically distinct but functionally synergistic innate immune agonists for dual pathway activation in humanized mouse models. Specifically, our immunomodulatory NPs (immuno-NPs) co-deliver agonists of the stimulator of interferon (IFN) genes and Toll-like receptor 4 pathways. Together, dual pathway activation in target cells in the TME by immuno-NPs promotes the synergistic production of type I IFNs and other proinflammatory cytokines that powerfully remodel the cytokine milieu. We show that immuno-NPs can be delivered safely in the systemic blood circulation for deposition in the perivascular space of neuroblastoma primary tumors and metastases. Their broad uptake across immune cells, endothelial cells, and even tumor cells drives significant immune activation and restructuring of the cytokine milieu of the TME. We also demonstrate a pivotal role for otherwise exhausted CD8+ T cells that are local and already infiltrating the tumor. Immuno-NP-mediated rescue of this local T-cell subset is chiefly responsible for the acute clearance responses that may be essential for treatment efficacy in aggressive cancers like high-risk neuroblastoma. Taken together, our findings make a strong case for the use of pathogen-inspired, multi-innate pathway-activating therapies, such as immuno-NPs, for high-risk neuroblastoma and other solid tumor malignancies that urgently warrant effective TME remodeling approaches.

  PublisherOA PDFDOI

• Abstract A119: Designing tumor-targeting nanoparticles for the delivery of therapeutic payloads in pancreatic ductal adenocarcinoma

  Cancer Research · 2025-09-28

  articleSenior author

  Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a minimal five-year survival rate. A hallmark of PDAC is the prevalence of oncogenic mutations in the KRAS gene, observed in more than 90% of the cases. The KRAS oncogene plays a critical role in disease initiation and progression, and its signaling network represents a major target for therapeutic intervention. Our previous studies have shown that the combination of MEK1/2 and CDK4/6 inhibitors facilitates vascular remodeling that augments drug delivery and T cell immune surveillance through induction of a senescence-associated secretory phenotype (SASP). While combined MEK1/2 and CDK4/6 inhibition can reduce tumor growth in preclinical models, it is not sufficient to produce long-term tumor responses, and the toxicities associated with MEK inhibitors have limited their clinical advancement. Here, we designed novel lipid nanoparticles (NPs) coloaded with the MEK1/2 and CDK4/6 inhibitors for enhanced anti-tumor efficacy. The incorporation of ionizable lipids into the NPs promotes stable encapsulation and triggers pH-dependent dissolution of the NPs, allowing endosomal rupture and cargo release into the cytosol. In vitro, the NPs inhibited the downstream effectors of the RAS signaling pathway, leading to enhanced SASP factor expression. In an orthotopic KPC PDAC model, the NPs exhibited tumor-homing capability, resulting in a greater reduction in the phosphorylation of the retinoblastoma protein (p-RB) and the proliferation marker, Ki67, compared to administration of the free drugs. To further achieve cell-specific delivery, the NPs were conjugated to a linear peptide with a high affinity for epidermal growth factor receptor (EGFR)—a receptor overexpressed in up to 85% of PDAC cells but not normal adjacent pancreas tissue. The targeted NPs contributed to a greater NP uptake compared to untargeted NPs, leading to an increase in SASP factor expression in vitro. Similarly, systemic administration of targeted-NPs was significantly more effective in tumor growth reduction, supported by the suppression of p-RB and Ki67, as compared to untargeted NPs or free drugs. In addition, treatment with the targeted NPs led to an increase in innate natural killer (NK) cell and dendritic cell (DC) infiltration and activation, which was not observed previously with MEK and CDK4/6 inhibitors. Importantly, the targeted NPs minimized lymphocytopenia, neutrophilia, and off-target effects on RAS signaling in the colon typically caused by these inhibitors following systemic administration. Therefore, PDAC cell-targeted NPs allow enhanced anti-tumor efficacy of RAS pathway inhibitors while minimizing toxicity that has constrained their clinical implementation. Given their versatile properties, NPs can be engineered to encapsulate other inhibitors, including the RAS(ON) inhibitors currently being evaluated in clinical trials for PDAC patients. Furthermore, we anticipate that these NPs can be rationally coupled with innate immunotherapies to achieve more robust and long-lived anti-tumor effects. Citation Format: Haruka Mori, Kelly D. DeMarco, Hadiya K. Giwa, Ronnie W. Dinnell, Griffin I. Kane, Chaitanya N. Parikh, Miranda B. Diaz-Infante, Marcus Ruscetti, Prabhani U. Atukorale. Designing tumor-targeting nanoparticles for the delivery of therapeutic payloads in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr A119.

  PublisherDOI

• Multiplexed cytokine and antigen mRNA administration generates durable anti-tumor immunity against pancreatic cancer

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-14

  preprintOpen access

  ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) remains a devastating malignancy characterized by limited therapeutic options for advanced disease. Immunotherapy, in particular, has had dismal success rates in the PDAC due to a tumor microenvironment (TME) that contributes to immune exclusion and poor drug delivery. Many cytokines necessary for Natural Killer (NK) and T cell chemotaxis, activation, and cytotoxicity are absent in the PDAC TME. Despite their early success, cytokine therapies have largely failed in the treatment of solid tumors as a result of the lack of efficacy of single cytokine administration and toxicities from systemic delivery. To overcome these limitations, we designed multiplexed mRNA cocktails encoding diverse interleukins, chemokines, and interferons for intratumoral delivery. Administration of a cytokine-encoding mRNA mixture into mice with orthotopically transplanted PDAC tumors achieved robust yet transient cytokine expression locally in the PDAC TME, leading to NK cell and CD8 + T cell immunity and reduced tumor growth and fibrosis in multiple mouse models. Combining cytokine mRNAs with those encoding tumor-associated antigens further activated CD8 + T cell-mediated tumor control and enhanced survival after just a single dose in PDAC-bearing mice. Remarkably, lipid-based nanoparticle (NP) encapsulation of an all-in-one cytokine and antigen mRNA cocktail allowed safe systemic administration and local delivery of these immunogenic signals to autochthonous PDAC tumors in genetically engineered mouse models, culminating in complete tumor responses in 50% of animals. These results suggest that multiplexed mRNA approaches to delivering cytokine signals and antigens generally absent in the TME could pave the way for an effective immunotherapy for PDAC.

  PublisherOA PDFDOI

• Abstract A088: Dual-agonist loaded "super adjuvant” nanoparticles as a modular platform for cancer vaccination

  Cancer Immunology Research · 2025-02-23

  articleSenior author

  Abstract We report on the utility of a “super adjuvant” nanoparticle (NP) system as a modular, customizable platform for next-generation cancer vaccination. Using nanomaterials engineering technology, we aim to harness the effective adjuvanticity of whole-pathogen vaccines combined with the safety profile of subunit vaccines. This lipid-based platform uniquely co-encapsulates agonists of the Stimulator of Interferon Genes (STING) and Toll-like Receptor 4 (TLR4) pathways to promote synergistic production of Type I interferons and other proinflammatory cytokines in antigen-presenting dendritic cells (DCs) and macrophages. Compared to empty NPs and free agonists, dual-adjuvant NPs promoted increased antigen processing and presentation, drained efficiently to nearby lymph nodes, increased polyfunctional T and B cells, and improved tumor-free outcomes upon vaccination and subsequent challenge with multiple aggressive tumor cells. Citation Format: Griffin I Kane, Tiana E Naylor, Christina F Lusi, Meghan L Brassil, Kim Wigglesworth, Haruka Mori, Prabhani U Atukorale. Dual-agonist loaded "super adjuvant” nanoparticles as a modular platform for cancer vaccination [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A088.

  PublisherDOI

• Abstract A093: Multiplexed cytokine and antigen mRNA administration generates durable anti-tumor immunity against pancreatic cancer

  Cancer Research · 2025-09-28

  article

  Abstract Pancreatic ductal adenocarcinoma (PDAC) remains a devastating malignancy characterized by limited therapeutic options for advanced disease. Immunotherapy in particular has had dismal success rates in the PDAC due to a tumor microenvironment (TME) that contributes to immune exclusion and poor drug delivery. Many cytokines necessary for Natural Killer (NK) and T cell chemotaxis, activation, and cytotoxicity are absent in the PDAC TME. Despite their early success, cytokine therapies have largely failed in the treatment of solid tumors as a result of the lack of efficacy of single cytokine administration and toxicities from systemic delivery. To overcome these limitations, we designed multiplexed mRNA cocktails encoding diverse interleukins, chemokines, and interferons for intratumoral delivery. Administration of a cytokine-encoding mRNA mixture into mice with orthotopically transplanted PDAC tumors could achieve robust yet transient cytokine expression locally in the PDAC TME, leading to NK cell and CD8+ T cell immunity and reduced tumor growth and fibrosis in multiple mouse models. Combining cytokine mRNAs with those encoding tumor-associated antigens could further activate CD8+ T cell-mediated tumor control and enhanced survival after just a single dose in PDAC-bearing mice. Remarkably, lipid-based nanoparticle (NP) encapsulation of an all-in-one cytokine and antigen mRNA cocktail allowed safe systemic administration and local delivery of these immunogenic signals to autochthonous PDAC tumors in genetically engineered mouse models, culminating in complete tumor responses in 50% of animals. These results suggest that multiplexed mRNA approaches to delivering cytokine signals and antigens generally absent in the TME could pave the way for an effective immunotherapy for PDAC. Citation Format: Chaitanya Naimesh Parikh, Kelly De Marco, Griffin Kane, Nikita Bhalerao, Ronnie Dinnell, Hadiya Giwa, Zhao Zhen, Lin Zhou, Katherine Murphy, Loretah Chibaya, Youwei Qiao, Wen Xue, Haruka Mori, Brian Lewis, Jason Pitarresi, Prabhani Atukorale, Marcus Ruscetti. Multiplexed cytokine and antigen mRNA administration generates durable anti-tumor immunity against pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr A093.

  PublisherDOI

• Super-adjuvant nanoparticles for platform cancer vaccination

  Cell Reports Medicine · 2025-10-01 · 1 citations

  articleOpen accessSenior author

  We report on the utility of a "super-adjuvant" nanoparticle (NP) system as a modular, customizable platform for next-generation cancer vaccination. Using nanomaterials engineering technology, we aim to harness not only the effective adjuvanticity of whole-pathogen vaccines, but also the safety of subunit vaccines. Our lipid-based NP platform co-encapsulates agonists of the stimulator of interferon genes (STING) and Toll-like receptor 4 (TLR4) pathways to promote synergistic production of type I interferons and other proinflammatory cytokines in innate antigen-presenting dendritic cells and macrophages. Compared to empty NPs and free agonists, dual-adjuvant NPs administered with antigenic peptides or tumor cell lysate promote increased antigen processing and presentation, drain efficiently to nearby lymph nodes, increase polyfunctional tumor-specific T and B cells, and improve tumor-free outcomes upon vaccination and subsequent challenge with multiple aggressive tumor cells.

  PublisherOA PDFDOI

• Abstract A043: Combination of immune agonist-containing nanoparticles and sitravatinib to treat high-risk neuroblastoma

  Cancer Immunology Research · 2025-02-23

  articleSenior author

  Abstract High-risk neuroblastoma has a detrimental diagnosis for children, with a 50% 5-year survival rate driven primarily by metastasis, the largest hurdle for clinical treatment. Here, we present the combination of orally administered sitravatinib with intravenously delivered dual immune agonist-containing lipid-based nanoparticles (immuno-NPs) as a systemic immunotherapy. Immuno-NPs are loaded with monophosphoryl lipid a, a toll-like receptor 4 agonist, and cyclic di-GMP, a stimulator of interferon genes agonist. Uptake of these agonists by antigen-presenting cells promotes the production of type 1 interferons in the tumor microenvironment (TME), engaging innate immune cells within and around the TME to drive the characteristically cold, immunosuppressive neuroblastoma into a hot, immune-infiltrated state. This shift, the mounting of a vigorous immune response, leads to the recruitment of the effector cells to the tumor and metastatic sites which current treatment modalities struggle to accomplish. The second modality, sitravatinib, is a receptor tyrosine kinase inhibitor targeting multiple receptor tyrosine kinases including discoidin domain receptor 2 (DDR2); previous research has implicated this receptor as an auxiliary protein involved in metastasis for breast cancer. Through extrapolation, we believe DDR2 plays a similar role in neuroblastoma through its modulation and subsequent linearization of collagen fibers in the extracellular environment facilitating metastasis and augmentation of the epithelial-mesenchymal transition (EMT). Furthermore, sitravatinib has been suggested to alleviate immune suppression holding promise for synergistic impact when combined with immuno-NP treatment. We have previously tested our combination immunotherapy in the syngeneic 9464D-GD2 tumor model and humanized mouse SH-SY5Y orthotopic model. Our results have demonstrated the promise of this combination: an increase in the survival time of combination-treated groups and a reduction of tumor volume. Additionally, we have expanded to conducting survival studies of our combination immunotherapy in melanoma and breast cancer models, demonstrating the utility of our immunotherapy for other highly metastatic cancers. Our ongoing mechanistic studies include quantification of EMT inhibition in the primary tumor, collagen remodeling in the TME, and reversal of immune cell suppression after therapy. Our current data supports a programmatic shift to a hot TME signified by the increased presence of cytotoxic t cells within the tumor. In conjunction, we have preliminary data suggesting the efficacy of our immunotherapy in driving cells toward an epithelial phenotype confirmed by adhesion protein expression. We hypothesize our current mechanistic studies will confirm the linearization of collagen in the TME and its reversal in combination-treated groups. Herein, we have developed a combination immunotherapy platform with efficacy in treating high-risk neuroblastoma and other metastatic cancers and are elucidating its mechanism of action. Citation Format: Miranda B Diaz-Infante, Kim Wigglesworth, John Lukas, Griffin Kane, Meghan Brassil, Christina Lusi, Christian Alarcon, Jason Shohet, Prabhani U Atukorale. Combination of immune agonist-containing nanoparticles and sitravatinib to treat high-risk neuroblastoma [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A043.

  PublisherDOI

• Abstract B035: Nanoparticle delivery of innate immune agonists combines with senescence- inducing agents to mediate T cell control of pancreatic cancer

  Cancer Research · 2024-09-15

  article

  Abstract Pancreatic ductal adenocarcinoma has quickly risen to become the 3rd leading cause of cancer- related death. This is in part due to its fibrotic tumor microenvironment (TME) that contributes to poor vascularization and immune infiltration and subsequent chemo- and immunotherapy failure. Here we investigated an innovative immunotherapy approach combining delivery of STING and TLR4 innate immune agonists via lipid-based nanoparticles (NPs) co-encapsulation with senescence-inducing RAS-targeted therapies that can remodel the immune suppressive PDAC TME through the senescence-associated secretory phenotype. Treatment of transplanted and autochthonous PDAC mouse models with these regimens led to enhanced uptake of NPs by multiple cell types in the PDAC TME, induction of type I interferon and other pro-inflammatory signaling, increased antigen presentation by tumor cells and antigen presenting cells, and subsequent activation of both innate and adaptive immune responses. This two-pronged approach produced potent T cell-driven and Type I interferon-mediated tumor regressions and long-term survival in preclinical PDAC models dependent on both tumor and host STING activation. STING and TLR4-mediated Type I interferon signaling were also associated with enhanced NK and CD8+ T cell immunity in human PDAC. Thus, combining localized immune agonist delivery with systemic tumor-targeted therapy can synergize to orchestrate a coordinated Type I interferon-driven innate and adaptive immune assault to overcome immune suppression and activate durable anti-tumor T cell responses against PDAC. Citation Format: Kelly D DeMarco, Loretah Chibaya, Christina F Lusi, Griffin I Kane, Meghan L Brassil, Chaitanya N Parikh, Katherine C Murphy, Shreya R Chowdury, Junhui Li, Boyang Ma, Tiana E Taylor, Julia Cerrutti, Haruka Mori, Miranda Diaz-Infante, Jessica Peura, Jason R Pitarresi, Lihua Julie Zhu, Katherine A Fitzgerald, Prabhani U Atukorale, Marcus Ruscetti. Nanoparticle delivery of innate immune agonists combines with senescence- inducing agents to mediate T cell control of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B035.

  PublisherDOI

• Abstract 4043: Nanoparticle-mediated combination therapy to synergistically harness Type I interferons and senescence in the pancreatic tumor microenvironment

  Cancer Research · 2024-03-22 · 1 citations

  article1st authorCorresponding

  Abstract We seek to combine a unique innate immunomodulatory nanoparticle (NP) system with RAS inhibitors for a multi-faceted therapy that mitigates the formidable drug delivery challenges in pancreatic ductal adenocarcinoma (PDAC). PDAC has quickly risen to the third most deadly cancer largely due to its fibrotic, desmoplastic, and immunosuppressive tumor microenvironment (TME) that limits delivery and efficacy of chemo- and immunotherapeutics. We have engineered unique lipid-based NPs that co-encapsulate agonists of the Stimulator of Interferon Genes (STING) and Toll-like Receptor 4 (TLR4) pathways. NPs can be safely delivered in the systemic blood circulation to achieve TME deposition, uptake by innate antigen-presenting cells (APCs), and robust, synergistic production of Type I interferons by dual STING/TLR4 activation. Here, we hypothesize that combination therapy of proinflammatory NPs with tumor senescence-inducing RAS inhibitors, tremetinib and palbociclib, will not only augment CD8+ T cell recruitment to the TME but enhance their sustained activation by mitigating local immunosuppression. In mice bearing orthotopic transplant KPC tumors or KPC GEMMs, combination NP/inhibitor treatment promoted significant NP delivery to tumors, APC and natural killer (NK) cell activation, and CD8+ T cell-mediated clearance, compared to monotherapies and untreated controls. Unexpectedly and strikingly, these studies also showed that, besides innate immune cells, combination therapy also promoted Type I interferon and other proinflammatory cytokine production by PDAC tumor cells, which are otherwise notoriously unresponsive to current state-of-the-art treatments. Further, in KPC GEMMs, 25% of mice exhibited apparent complete responses following combination treatment, which, to our knowledge, is challenging to achieve in this model. Current studies include the mechanistic elucidation of immune- and tumor-intrinsic factors that govern efficacy of our combination therapy. In conclusion, these findings strongly corroborate the use of this NP-based system as a platform therapy for similar drugs and across other aggressive cancers. They also strongly make the case for the rational design of combination therapies to achieve synergistic therapeutic outcomes with minimal systemic toxicities. Citation Format: Prabhani Atukorale, Marcus Ruscetti, Loretah Chibaya, Christina Lusi, Kelly DeMarco, Griffin Kane, Meghan Brassil, Chaitanya Parikh, Katherine Murphy. Nanoparticle-mediated combination therapy to synergistically harness Type I interferons and senescence in the pancreatic tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4043.

  PublisherDOI

• Nanocarrier design for pathogen-inspired innate immune agonist delivery

  Trends in Immunology · 2024-08-26 · 6 citations

  reviewOpen accessSenior author

  In complex diseases such as cancer, modulating cytokine signatures of disease using innate immune agonists holds therapeutic promise. Novel multi-agonist treatments offer tunable control of the immune system because they are uniquely pathogen inspired, eliciting robust antitumor responses by promoting synergistic cytokine responses. However, the chief strategic hurdle is ensuring multi-agonist delivery to the same target cells, highlighting the importance of using nanomaterial-based carriers. Here, we place nanocarriers in center stage and review the delivery hurdles related to the varying extra- and intracellular localizations of innate immune receptors. We discuss a range of nanomaterials used for multi-agonist delivery, highlighting their respective benefits and drawbacks. Our overarching stance is that rational nanocarrier design is crucial for developing pathogen-inspired multi-agonist immunotherapies.

  PublisherOA PDFDOI

Frequent coauthors

• Griffin Kane

  University of Massachusetts Chan Medical School

  30 shared

• Christina F. Lusi

  University of Massachusetts Chan Medical School

  29 shared

• Efstathios Karathanasis

  Case Western Reserve University

  24 shared

• Darrell J. Irvine

  Scripps Research Institute

  23 shared

• Meghan L. Brassil

  Amherst College

  21 shared

• Gil Covarrubias

  Massachusetts Institute of Technology

  17 shared

• Taylor J. Moon

  13 shared

• Francesco Stellacci

  École Polytechnique Fédérale de Lausanne

  12 shared

Awards & honors

• NIH Trailblazer Award