SUMMARY: UCLA Researchers from the division of Immunology in the David Geffen School of Medicine have developed an improved method of stimulating anti-tumor T-cells for use in cancer immunotherapy. BACKGROUND: Cancer immunotherapy, a therapeutic strategy whereby a patient’s own immune system is reequipped to attack cancer cells, promises more effective treatments against cancers without many of the off-target toxicity concerns associated with other curative methods currently in use. In one area of development: adoptive T-cell therapy, a cancer vaccine can be generated by stimulating a patient’s own cytotoxic T-cells to expand and kill cancer cells. This allows for more specific targeting of cancer cells by recognizing antigens associated exclusively with malignant cells. Unfortunately, identification of these cancer antigens, and subsequently raising and stimulating T-cells against these antigens, remains a primary barrier in the widespread use of T-cells for immunotherapy in the clinic. Methods currently used can require slow genetic and proteomic analysis of tumor samples to identify antigen targets. For this field to advance, there is a need for technology that enables highly efficient stimulation of T-cells against patient-specific antigens on shorter timescales. INNOVATION: Here, researchers present a novel microparticle-based approach to stimulating T-cells against patient-specific antigens, without the requirement for laborious and time-intensive genetic and computational methods. The technology makes use of components from multiple sources, including the patient’s own tumor, to promote the effectiveness and specificity of the stimulated T-cells. The microparticles described herein are comprised of tumor antigens, costimulatory components, immunoregulatory molecules and a structural polymer. Importantly, tumor antigens can be identified and produced in vitro or sourced directly from the patient’s tumor, leading to increased flexibility in design. In vitro production of all other components of the microparticle allows for a potentially high degree of multi-functionality and efficiency. In the stimulation process, T-cells are acquired directly from the patient’s blood, stimulated ex vivo and subsequently purified from microparticles and returned to the patient. Notably, these microparticles and all components can be produced using established molecular techniques. POTENTIAL APPLICATIONS: • Stimulation of T-cells with patient-specific tumor antigen for cancer immunotherapy. ADVANTAGES: • Rapid turnaround from diagnosis to vaccine development. • Bypasses inefficient computational/genetic neoantigen identification. • Allows for patient-specific tumor antigen incorporation into microparticles—is highly modular. • Formulation can be modulated to induce or repress T-regulatory cells. DEVELOPMENT-TO-DATE: Proven principle: researchers have demonstrated efficacy of microparticles in stimulating T-cell mediated tumor clearance in mouse models.