CPMV-Polymer Devices to Enhance the Outcomes of Intratumoral Immunotherapy - CPMV-Polymer Devices to Enhance the Outcomes of Intratumoral Immunotherapy Steinmetz (PI) and her colleagues have developed a plant virus nanoparticle immunotherapy that activates innate immune cells in the tumor microenvironment (TME) to launch adaptive, systemic, and durable antitumor immunity. Specifically, we found that nanoparticles based on cowpea mosaic virus (CPMV) stimulate a potent antitumor response in solid tumor mouse models and in canine cancer patients. Intratumoral immunotherapy CPMV overcomes immunosuppression within the TME launching adaptive antitumor immunity and immunological memory to prevent cancer recurrence. CPMV interacts with the immune system in a multivalent manner, resulting in a cascade of events boosted by avidity to achieve unprecedented potency. The intratumoral immunotherapy development pipeline is advancing quickly, but its effectiveness faces challenges, necessitating better delivery methods. Key issues include: (1) Large tumors often need more drugs or multiple injections, complicating procedures and possibly affecting therapy results due to variability. (2) High fluid pressure in tumors, caused by factors like vascular issues and confined cell growth, can impede drug delivery and even push drugs out of the tumor. (3) Frequent dosing can discomfort patients (and/or owner’s when patients are dogs), affecting their willingness to continue treatment. Therefore, we propose slow-release CPMV-polymer blend formulations for delivery as injectable devices. CPMV will be incorporated into polymer blends by applying scalable hot melt extrusion (HME) processing technology. Pokorski (MPI) is an expert in HME processing of biologics and our preliminary data confirm the structural and biological stability of CPMV released from the device technology. Finally, protein/polymer melts will be converted into injectable implants and microparticles using routinely available milling and molding equipment. We will fulfill the following aims: First, we will formulate CPMV-laden slow- release devices, establish and tune the release rates, confirm the structural integrity and biological activity released CPMV from the delivery technology. Second, we will perform clinical testing to establish efficacy, mechanism of action, and safety as a function of dose and delivery device. While the approach and CPMV intratumoral immunotherapy is tumor-agnostic, we will focus on metastatic breast cancer. To mimic a patient population with different subtypes of breast cancer, we will use immune-competent mouse models of metastatic disease including models of triple negative breast cancer, HER2+ and ER+/HER2- tumors. Third, as a prelude toward translation, we will perform a phase 0 canine trial enrolling canine patients with non- metastatic and metastatic mammary tumors; in collaboration with Co-I Peña. Companion dogs with spontaneous tumors provide a uniquely powerful resource that can be used for translational research as well as treatment of someone’s well-loved pet.
