Cross-presentation is an essential bridge between the innate and adaptive arms of the immune system where antigen presenting cells (APCs) prime cytotoxic T cell responses. We have recently identified cross-presentation as a mechanism by which solid tumors present exogenous antigens. We therefore hypothesized that multiple myeloma would be capable of cross-presentation as these cells are derived from B cells, known APCs. We explored the capacity of multiple myeloma to cross-present PR1, a human leukocyte antigen (HLA)-A2 nonameric peptide that is derived from neutrophil elastase (NE) and proteinase 3 (P3), and the ability to treat multiple myeloma using PR1-targeting immunotherapies. Here we demonstrate that multiple myeloma cells lack endogenous NE and P3 expression, possess the ability to take up exogenous NE and P3 and cross-present PR1. This process employs the cytosolic antigen presentation machinery including the proteasome, Golgi, and TAP. Subsequent PR1 cross-presentation renders multiple myeloma cells susceptible to PR1-CTL and anti-PR1/HLA-A2 antibody, both in vitroand in vivo. To our knowledge, this is the first report of multiple myeloma cross-presenting tumor antigens. Collectively, our data demonstrate that PR1 is a novel tumor antigen in multiple myeloma and can be effectively targeted using PR1-targeting immunotherapies. Our study suggests that the multiple myeloma antigen repertoire is much larger than previously appreciated, and that there is a new catalogue of potential immunotherapeutic targets in multiple myeloma that can be derived from exogenous antigens.
","abstract_html":"<p>Cross-presentation is an essential bridge between the innate and adaptive arms of the immune system where antigen presenting cells (APCs) prime cytotoxic T cell responses. We have recently identified cross-presentation as a mechanism by which solid tumors present exogenous antigens. We therefore hypothesized that multiple myeloma would be capable of cross-presentation as these cells are derived from B cells, known APCs. We explored the capacity of multiple myeloma to cross-present PR1, a human leukocyte antigen (HLA)-A2 nonameric peptide that is derived from neutrophil elastase (NE) and proteinase 3 (P3), and the ability to treat multiple myeloma using PR1-targeting immunotherapies. Here we demonstrate that multiple myeloma cells lack endogenous NE and P3 expression, possess the ability to take up exogenous NE and P3 and cross-present PR1. This process employs the cytosolic antigen presentation machinery including the proteasome, Golgi, and TAP. Subsequent PR1 cross-presentation renders multiple myeloma cells susceptible to PR1-CTL and anti-PR1/HLA-A2 antibody, both <em>in vitro</em>and <em>in vivo</em>. To our knowledge, this is the first report of multiple myeloma cross-presenting tumor antigens. Collectively, our data demonstrate that PR1 is a novel tumor antigen in multiple myeloma and can be effectively targeted using PR1-targeting immunotherapies. Our study suggests that the multiple myeloma antigen repertoire is much larger than previously appreciated, and that there is a new catalogue of potential immunotherapeutic targets in multiple myeloma that can be derived from exogenous antigens.</p>","abstract_has_math":false,"creators":["Perakis, Alexander A.","https://orcid.org/0000-0002-8172-7281
"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Gheath Al-Atrash, D.O., Ph.D.","Jeffrey J. Molldrem, M.D.","Michelle C. Barton, Ph.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-05-01T07:00:00Z","date_published":"2019-05-01T07:00:00Z","updated_at":"2026-07-24T05:49:16Z","subjects":["multiple myeloma","immunotherapy","cross-presentation","antibody","Biology","Cancer Biology","Immunology and Infectious Disease","Medicine and Health Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/949","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Gheath Al-Atrash, D.O., Ph.D.","Jeffrey J. Molldrem, M.D.","Michelle C. Barton, Ph.D."]},{"key":"dc:creator","label":"Author","values":["Perakis, Alexander A.","https://orcid.org/0000-0002-8172-7281
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"]},{"key":"dc:title","label":"Title","values":["Cross-Presentation Is A Source of Tumor Antigens For Multiple Myeloma Immunotherapy"]}]}],"canonical_facts":{"dc:contributor":["Gheath Al-Atrash, D.O., Ph.D.","Jeffrey J. Molldrem, M.D.","Michelle C. Barton, Ph.D."],"dc:creator":["Perakis, Alexander A.","https://orcid.org/0000-0002-8172-7281
"],"dc:date.available":["2020-05-09T07:00:00Z"],"dc:description.abstract":["Cross-presentation is an essential bridge between the innate and adaptive arms of the immune system where antigen presenting cells (APCs) prime cytotoxic T cell responses. We have recently identified cross-presentation as a mechanism by which solid tumors present exogenous antigens. We therefore hypothesized that multiple myeloma would be capable of cross-presentation as these cells are derived from B cells, known APCs. We explored the capacity of multiple myeloma to cross-present PR1, a human leukocyte antigen (HLA)-A2 nonameric peptide that is derived from neutrophil elastase (NE) and proteinase 3 (P3), and the ability to treat multiple myeloma using PR1-targeting immunotherapies. Here we demonstrate that multiple myeloma cells lack endogenous NE and P3 expression, possess the ability to take up exogenous NE and P3 and cross-present PR1. This process employs the cytosolic antigen presentation machinery including the proteasome, Golgi, and TAP. Subsequent PR1 cross-presentation renders multiple myeloma cells susceptible to PR1-CTL and anti-PR1/HLA-A2 antibody, both in vitroand in vivo. To our knowledge, this is the first report of multiple myeloma cross-presenting tumor antigens. Collectively, our data demonstrate that PR1 is a novel tumor antigen in multiple myeloma and can be effectively targeted using PR1-targeting immunotherapies. Our study suggests that the multiple myeloma antigen repertoire is much larger than previously appreciated, and that there is a new catalogue of potential immunotherapeutic targets in multiple myeloma that can be derived from exogenous antigens.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/949"],"dc:subject":["multiple myeloma","immunotherapy","cross-presentation","antibody","Biology","Cancer Biology","Immunology and Infectious Disease","Medicine and Health Sciences"],"dc:title":["Cross-Presentation Is A Source of Tumor Antigens For Multiple Myeloma Immunotherapy"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:49:16Z"}