{"doi":"10.1136/jitc-2022-sitc2022.0256","title":"256 <i>In vivo</i> expansion of endogenous antigen-specific CD8+ T cells using artificial T-cell stimulating microparticles","abstract":"<h3>Background</h3> T cell-based immunotherapies such as chimeric antigen receptor T cell therapy (CAR T), have seen some clinical success; however, these therapies are still currently limited to a select few cancer types and have price tags that further limit accessibility for patients. Here, we create a novel biomaterials-based platform for the <i>in vivo</i> activation of naïve, antigen-specific T cells, removing the need for expensive and lengthy <i>ex vivo</i> expansion steps. <h3>Methods</h3> Thiol-modified HA is cross-linked with PEDGA in the presence of thiol-modified signals 1 (here, KbOVA) and 2 (anti CD28).<sup>1</sup> The cross-linked gel is passed through a mesh to form microparticles (MPs) (figure 1A). MPs are mixed with naïve B6 CD8+ T cells and injected subcutaneously into mice. Eight days after injection, target cells expressing OVA antigen are injected i.v. On day 9, mice are sacrificed and analyzed for enrichment of antigen-specific cells and killing of target cells. MPs were also tested therapeutic tumor model, in which MC-38 OVA tumor cells were injected on day 0 and naïve OT I CD8s plus MPs were injected on day 6. <h3>Results</h3> Nine days after co-injecting naïve B6 CD8+ T cells with KbOVA MPs, we can detect a significant enrichment of OVA-specific T cells via flow cytometry (figure 1B). Cells expanded <i>in vivo</i> showed significant and robust killing of target splenocytes (figure 1C). In the MC-38 OVA cancer treatment model, injection of naïve OT I CD8+ T cells with OVA MPs increased survival compared with naïve OT I CD8+ cells injected with blank MPs (figure 1D). <h3>Conclusions</h3> We have developed an injectable, LN-mimicking MP platform that incorporates T-cell activation signals and critical ECM cues of the LN. These MPs are capable of expanding antigen-specific T cells from a fully endogenous B6 repertoire, and these cells are able to robustly kill target splenocytes as well as reduce tumor growth and extend survival in a therapeutic cancer model. Developing a system for the <i>in vivo</i> activation of antigen-specific T cells reduces both cost of T cell-based therapies as well as the time to treatment for patients. <h3>Acknowledgements</h3> NKL is supported by the NSF GRFP and NIH F31 Fellowships. <h3>Reference</h3> Hickey JW, Dong Y, Chung JW, Salathe SF, Pruitt HC, Li X, Chang C, Fraser AK, Bessell CA, Ewald AJ, Gerecht S, Mao H, Schneck JP. Engineering an Artificial T-Cell Stimulating Matrix for Immunotherapy. <i>Adv Mater</i>. 2019; Apr 10;1807359.","journal":"Regular and Young Investigator Award Abstracts","year":2022,"id":312886,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":808844,"name":"John M. Hickey","orcid":"0000-0001-5675-3974","position":1,"is_corresponding":false},{"id":1011174,"name":"Hajin Sim","orcid":null,"position":2,"is_corresponding":false},{"id":259708,"name":"Hai‐Quan Mao","orcid":"0000-0002-4262-9988","position":3,"is_corresponding":false},{"id":298449,"name":"Jonathan P. Schneck","orcid":"0000-0001-5346-2776","position":4,"is_corresponding":false},{"id":298448,"name":"Natalie K. Livingston","orcid":"0000-0002-0909-9284","position":0,"is_corresponding":true}],"reference_count":1,"raw_metadata":null,"created_at":"2026-07-19T00:33:40.460845Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}