Project Awardees
The Advanced Research Projects Agency for Health (ARPA-H) funds individual research projects that align with ARPA-H’s research focus areas but fall outside the scope of an ARPA-H program or initiative.
Projects are most often awarded through Mission Office Innovative Solution Openings (ISO) and historically through the Open BAA announcement. As of March 2024, ARPA-H is no longer accepting submissions for the Open BAA solicitation.
ARPA-H is pleased to announce the following project awardees.
CDTR: Stem Cell-Derived Thymus Rejuvenation
Thymmune Therapeutics’ Stem Cell-Derived Thymus Rejuvenation (CDTR) project aims to restore immune and endocrine function in patients lacking a functional thymus by using engineered stem cell-derived treatment. The thymus is an organ responsible for supporting normal immune cell development. The project is divided into two phases. The goal of the first phase is to use a combination of chemical and genetic factors to make best-in-class human induced pluripotent stem thymic epithelial cells (iPS-TECs) with capacity for supporting T lymphocytes (white blood cells) development in vivo. In the second phase, Thymmune plans to develop protocols for transplantation and long-term engraftment of iPS-TEC in animal models to achieve effective immune function, demonstrating a path towards using iPS-TEC to ultimately treat patients lacking functional thymus. Overall, Thymmune’s disease-agnostic approach to combat thymus dysfunction by bolstering immune responses against pathogens, cancer, and vaccines presents a potentially revolutionary means to reboot immunity. Thymmune has the potential to both rescue patients lacking a functional thymus from morbidity and mortality and addresses a crucial unmet need to rejuvenate immunity in the aging population.
HEART: Health Enabling Advancements through Regenerative Tissue Printing
Over 3 million patients in the United States need tissue transplants, with more than 100,000 patients on the national transplant waiting list. Unfortunately, many of these people die while waiting for a donated organ. The Health Enabling Advancements through Regenerative Tissue Printing (HEART) project proposes to advance multiple technologies, including the optimization of purity and scalability of human cells, improved 3D printing technology and speed, advances in computational modeling, and novel approaches to organ maturation and implantation. The end result is the 3D printing of a human heart in one hour. This ambitious project has the potential to revolutionize the fields of human tissue and organ printing through large advances across multiple technologies. HEART could create a world where a doctor could 3D print an organ for their patient instead of waiting for a donor, effectively ending waitlists for transplants. This advance would improve the lifespan and quality of life for many Americans and provide broader patient access across all communities.
THOR: Targeted Hybrid Oncotherapeutic Regulation
In the United States alone, over 19,000 women are expected to be diagnosed with ovarian cancer in 2024. An effective treatment could save over 8,000 American lives each year, yet like many solid tumors, ovarian cancer does not respond effectively to current immunotherapies. A revolutionary approach in the fight against ovarian cancer has emerged thanks to the convergence of several technological and medical innovations. This new effort, called Targeted Hybrid Oncotherapeutic Regulation (THOR), will create a compact device designed to trigger the immune system against tumors. The device will be implanted in proximity of the tumor and will house specialized cells responsible for producing and delivering therapeutic molecules. These molecules will activate the immune system both locally around the tumor site and throughout the body. Additionally, the device will incorporate advanced sensors to detect and monitor biomarkers of cancer. The integration of these two components in a single device will enable precise delivery of therapeutic doses tailored to each patient’s needs.
CODA: Mapping the Cancer and Organ Degradome Atlas to Unlock Synthetic Biomarkers for Multi-Cancer Early Detection
For most tumor types, there are currently no effective diagnostic tests for detecting most cancers at the earliest stages, when tumors are still localized and most responsive to treatment. Ongoing efforts that focus on native tumor-shed biomarkers face significant challenges, as these markers are often found in vanishingly small quantities in blood or other fluids. The CODA (Cancer and Organ Degradome Atlas) platform uses cutting-edge synthetic biology and cell engineering technologies to catalog cellular profiles unique to diseased cancer cells and leverages them to build bioengineered sensors that can be deployed inside the body to hunt for malignant cells. These biosensors use unique metabolic changes in tumor cells to drive the release of synthetic biomarkers that can reach high enough levels in biofluids to enable earlier cancer detection. This technology has the potential to produce a highly precise, accurate, and cost-effective test for multi-cancer early detection (MCED) that can identify common cancers earlier, when treatment can be most effective, and streamline clinical intervention when tumors are still small.
SPIKEs: Programmable Scalable Therapeutics for Immune-directed Cancer-killing
Cancer immunotherapy, which harnesses the body’s own immune system to attack tumor cells, holds great potential. However, this therapy is currently hampered by very high costs, long and involved preparation processes, and frequent inefficacy against solid tumors. The University of Missouri’s Synthetic Programmable bacteria for Immune-directed Killing in tumor Environments (SPIKEs) project aims to develop a new class of living cancer immunotherapy that that can effectively address these limitations. The SPIKEs platform utilizes genetically programmable bacteria designed to sense tumor-associated metabolites as an exquisitely precise homing mechanism and then deliver therapeutic payloads that activate immune-directed killing of solid tumor cells without the need for the long and costly processes currently used. Bacterial therapeutics carrying programmable genetic circuitry that allows safe tissue targeting, on-demand activation and clearance, and multiple therapeutic functions – including immune cell recruitment, activation, and targeting – represent an innovative, scalable, cost-effective, and accessible treatment modality for cancer.
CUREIT: Curing the Uncurable via RNA-Encoded Immunogene Tuning
More than 25 million Americans currently live with autoimmune disease, and almost two million are projected to be diagnosed with cancer in 2023. Immune dysregulation is an underlying component of not only cancer and autoimmune diseases, but also infectious diseases, transplant rejection, and other common medical conditions. Current methods of immune modulation used to treat and mitigate these conditions are often expensive or not completely effective. Curing the Uncurable via RNA-Encoded Immunogene Tuning (CUREIT) aims to address immune dysregulation by directly programming immune cell function. Advances in gene-encoded technology will be leveraged to develop a platform capability able to both enhance protective immune responses as well as modulate insufficient or ineffective immune profiles. CUREIT seeks to develop a disease-agnostic toolbox of methods and technologies, including the in vivo delivery of mRNA-based drugs, cell targeting lipid nanoparticles, and ex vivo modulation of immune cells. This technology has the potential to make significant advancements towards managing or eliminating many diseases and conditions affecting all ages and demographics, including diseases that are currently untreatable.