Multifunctional Immunotherapy Nanoparticle to Enable Innate Immunotherapy for Kidney Cancer
Abstract
Scientific Objective and Rationale: Immunotherapy options for metastatic kidney cancer are rapidly expanding, including five first-line treatment strategies for metastatic clear cell kidney cancer patients. These include immunotherapy activating the adaptive immune system (T-cells), targeted therapy directed against blood vessel formation, and the combination of both. However, complete responses are rare, and durable responses are even rarer. In order to enhance responses to immune checkpoint inhibitors, other immunotherapies to activate the innate immune system are currently under development. Natural killer (NK) cells are a significant part of the innate immune system. Recent publications show that NK cells play a complimentary role to T-cells in tumor cell killing, and therefore are a good target for developmental therapies. We have preliminary data that kidney tumors lacking in NK cell gene expression do not respond to immune checkpoint inhibitors as well as kidney tumors that do have NK cell gene expression. We have developed an innovative approach using nanoparticles to activate NK cells in a tumor-specific fashion. We propose to use the multifunctional immunotherapy nanoparticle (MINP) technology to activate NK cells targeted to metastatic renal cell carcinoma (RCC). We propose to develop MINPs that are targeted against RCC and evaluate these using mouse models and patient-derived tumor graft models of RCC. Our proposal thus addresses key KCRP area of emphasis of therapeutic development. Innovation: Our approach is innovative in several aspects. We are proposing to activate NK cells of the innate immune system to improve upon immunotherapy options for metastatic RCC. The MINPs tailored specifically to RCC tumors are innovative in using concepts important in bioengineering, tumor immunology, and clinical oncology. The proposed MINPs can target ccRCC, papillary RCC and potentially other histologies. Importantly, the MINPs will activate NK cells to specifically kill RCC tumors. Finally, the tumor-based and peripheral NK cell population may also provide a biomarker to track during treatment of these tumors. Clinical Applicability: The successful completion of this research will help many patients with metastatic RCC in developing a new class of immunotherapy therapeutic agents. This proposal will generate the preclinical data necessary to translate these new therapies to the clinical setting. There are pending patents for NK-cell activating MINP technology, and the patents has been licensed by Archimmune Therapeutics, a startup biotechnology company. The successful completion of these proposed studies may enable rapid clinical translation of MINP technology for renal cell carcinoma, within several years for clinical development. The MINP technology can also be tailored for different cancer types and could become a platform to develop NK-activating therapies for different tumor types of kidney cancers. Ultimately, we hope to improve immunotherapies for all kidney cancer patients including Veterans as well as the American public.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310516
Entities
People
- Andrew Wang
Organizations
- United States Army
- University of Texas Southwestern Medical Center