Nanoparticles Offer Revolutionary Approach to Treating Lupus and Blood Cancers by Retraining Immune System

Scientists at Johns Hopkins Medicine have developed simplified biodegradable nanoparticles that can "educate" the immune system to find and destroy disease-causing cells, offering new hope for autoimmune diseases and cancer treatment.

Johns Hopkins Medicine scientists have achieved a breakthrough in immunotherapy with the development of simplified biodegradable nanoparticles capable of reprogramming the immune system to target and eliminate diseased cells throughout the body. Published March 11 in Science Advances, this research represents a significant advancement over current CAR-T cell therapies, potentially making these treatments more accessible and affordable for patients with autoimmune diseases like lupus and blood cancers including leukemia and lymphoma.

The Challenge with Current Immunotherapy Approaches

Engineered immune cells have already demonstrated remarkable success in treating various blood cancers through CAR-T (chimeric antigen receptor T cell) therapy. This treatment works by extracting a patient's own immune T cells from their blood, engineering them in a laboratory to express specialized receptors that recognize and destroy cancer cells, and then infusing these modified cells back into the patient.

However, this process faces substantial limitations:

High Cost: Current CAR-T therapies cost hundreds of thousands of dollars per treatment
Time-Intensive Manufacturing: The ex vivo process requires weeks to isolate, engineer, and expand patient cells
Complex Logistics: Each treatment is personalized and must be manufactured individually
Limited Accessibility: Only specialized medical centers can perform these complex procedures

"These experiments were successful using just one dose of the nanoparticles, and an advantage of using an off-the-shelf therapy is the potential for scalable manufacture and broad accessibility, whereas current forms of CAR-T therapies are very expensive and time-consuming," explained Jordan Green, Ph.D., the Herschel L. Seder Professor of Biomedical Engineering at Johns Hopkins University School of Medicine.

A Simpler Design with Powerful Results

The Johns Hopkins team developed nanoparticles with a remarkably streamlined design requiring only three components, compared to five components in recent lipid-based nanoparticle approaches:

PBAE Polymer: Poly(beta-amino ester) polymer that biodegrades in water
PEG Lipid: Helps stabilize the nanoparticle structure
mRNA Cargo: Genetic instructions encoding anti-CD19 chimeric antigen receptors

The nanoparticle surface is decorated with anti-CD3 and anti-CD28 antibody molecules that help locate and stimulate T cells. Once inside these immune cells, the nanoparticles release mRNA cargo that instructs T cells to express receptors capable of detecting and destroying disease-causing B cells—the source of autoimmune conditions like lupus and various blood cancers.

Remarkable Efficacy in Animal Studies

The research team conducted comprehensive tests in healthy mice, yielding impressive results:

Twenty-Four Hours After Treatment:

95% of target B cells were depleted in circulating blood
Approximately 50% of B cells were destroyed in the spleen across all test subjects

One Week Post-Treatment:

B cells in blood returned to approximately 50% of their original quantity, suggesting the effect is potent yet potentially reversible

"These experiments demonstrate that targeted delivery of CAR-encoding mRNA is critical for eliciting a therapeutic effect," the researchers noted in their publication. The potency was achieved through ligand and CAR mRNA-mediated mechanisms, confirming the precision of the nanoparticle approach.

Understanding the Biological Challenge

Designing nanoparticles capable of reaching T cells throughout the bloodstream and organs presents significant scientific challenges compared to delivering therapeutics to localized sites like the eye.

"T cells naturally resist taking up nanoparticles, and even when internalization occurs, the cells often degrade and expel them," Green explained. "This makes biological sense—if T cells easily absorbed viral-like particles, viruses could hijack the immune system, as seen in HIV."

The team's solution mirrors rocket staging systems used for space travel. The nanoparticles employ a stepwise approach:

Targeting: Nanoparticles seek out and attach to T cells using anti-CD3 and anti-CD28 molecules
Stimulation: They activate and multiply T cells
Entry: Particles pass through the cell wall into T cells
Degradation: Internal nanoparticles degrade, releasing mRNA cargo

This multi-stage mechanism proved highly effective. In previous studies, approximately 10% of Johns Hopkins-developed nanoparticles successfully escaped cellular degradation compartments to deliver their genetic cargo—significantly higher than the 1-2% success rate of competing nanoparticle technologies.

Five Years of Collaborative Innovation

Achieving this breakthrough required five years of dedicated research collaboration between Green's expertise in polymer-based nanoparticles and immunology specialist Jonathan Schneck, M.D., Ph.D., whose work focused on developing artificial immune cells capable of stimulating other immune cells.

The team blended these complementary research streams to create a platform that combines the advantages of both lipid nanoparticles (LNPs) and polymeric nanoparticles (PNPs). Notably, the PBAE-based nanoparticles can be stored in frozen conditions or lyophilized (freeze-dried)—capabilities traditionally unavailable for LNP formulations. These processing differences carry substantial translational implications for clinical settings where healthcare providers must handle and administer nanoparticles under varying storage and supply chain conditions.

Clinical Implications and Future Directions

The Johns Hopkins research team has recently been named as collaborators by biotechnology company ImmunoVec on a more than $40 million grant from the Advanced Research Projects Agency for Health (ARPA-H) to further develop these cell engineering tools.

The researchers aim to continue refining the nanoparticles with several optimization goals:

Enhanced Specificity: Better tailoring to diseased B cells while sparing healthy cells
Dose Control: Ability to dial up or down T-cell stimulation levels based on patient needs
Broader Applications: Testing in additional B cell-related malignancies and autoimmune conditions

"This research advances the field of engineering immune cells within a patient's own body to combat cancers and autoimmune diseases," said the team. Future investigations in different B cell-based malignancies spanning both murine and human models of cancer and autoimmune diseases are currently underway.

Funding and Institutional Support

This groundbreaking research received support from multiple prestigious sources:

National Institutes of Health: Grant numbers P41EB028239, R01CA281143, R37CA246699, R56DK137420, R21AI176764, F31CA284859
National Science Foundation
Johns Hopkins Translational ImmunoEngineering Center: A National Center for Biomedical Imaging and Bioengineering innovating biotechnologies to modulate the immune system

Additional Johns Hopkins scientists who contributed to this research include Manav Jain, Savannah Est-Witte, Sydney Shannon, Sarah Neshat, Xinjie Yu, Sydney Dunham, Tina Tian, Leonardo Cheng, Jawaun Harris, Max Konig, and Stephany Tzeng.

Scientific Reference

Jain, M., et al. (2026). Biodegradable targeted polymeric mRNA nanoparticles enable in vivo CD19 CAR T cell generation and lead to B cell depletion. Science Advances. DOI: 10.1126/sciadv.adz1722. https://www.science.org/doi/10.1126/sciadv.adz1722

References

Johns Hopkins Medicine. (2026, March 11). Johns Hopkins scientists engineer nanoparticles able to seek and destroy diseased immune cells. EurekAlert!. https://e3.eurekalert.org/news-releases/1119121
Genetic Engineering & Biotechnology News. (2026, March 11). Nanoparticles Trigger In Vivo CAR T Cell Generation to Eliminate B Cells. https://www.genengnews.com/topics/cancer/nanoparticles-trigger-in-vivo-car-t-cell-generation-to-eliminate-b-cells/
News-Medical. (2026, March 11). Simplified nanoparticles "educate" the immune system to find and destroy disease-causing cells. https://www.news-medical.net/news/20260311/Simplified-nanoparticles-educate-the-immune-system-to-find-and-destroy-disease-causing-cells.aspx

Disclaimer: This article is for informational purposes only and does not constitute medical advice. The research discussed is in early stages, having been tested primarily in animal models. Always consult with qualified healthcare professionals before making any health decisions. New therapies require extensive clinical trials before becoming widely available to patients.

Published by HealthTips Team | March 14, 2026 | Category: Immune System