Young donor white blood cell immunotherapy induces extensive tumor necrosis in advanced-stage solid tumors
Background: In the past decade, a variety of immunotherapy approaches focused predominantly on the adaptive immune system have shown unprecedented responses in patients with advanced-stage malignancies. However, studies in spontaneous regression/complete resistance (SR/CR) mice and humans have shown...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-10-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844017316936 |
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| author | Dipnarine Maharaj Pedro G. Vianna Wendy Ward Anthony J. Messina Trevor Rayborn Jacqueline V. Gouvea Richard D. Hammer Zheng Cui |
| author_facet | Dipnarine Maharaj Pedro G. Vianna Wendy Ward Anthony J. Messina Trevor Rayborn Jacqueline V. Gouvea Richard D. Hammer Zheng Cui |
| author_sort | Dipnarine Maharaj |
| collection | DOAJ |
| description | Background: In the past decade, a variety of immunotherapy approaches focused predominantly on the adaptive immune system have shown unprecedented responses in patients with advanced-stage malignancies. However, studies in spontaneous regression/complete resistance (SR/CR) mice and humans have shown a novel innate cancer-killing activity mediated by granulocytes, which is completely transferable for prevention or therapy against established malignancies. Methods: Three patients with advanced, relapsed or refractory solid tumors for which no standard therapy was available or was refused were enrolled into this ongoing combined phase I/II open label clinical trial testing the safety, dose tolerance, and possible antineoplastic efficacy of sequential infusions of HLA-mismatched non-irradiated allogeneic white cells (68–91% granulocytes) collected by leukapheresis from young, healthy donors (age 18–35) following mobilization with granulocyte colony stimulating factor (G-CSF) and dexamethasone. Results: Besides fevers and flushing, no infusional toxicities were observed. All patients remained clinically stable following infusions with mild cytokine release syndrome and no evidence of transfusion-associated graft-versus-host disease, acute tumor lysis syndrome,or transfusion-associated acute lung injury. Pathological examination of all cases post-mortem revealed extensive tumor necrosis up to 80% in patients 1–2, 40–50% in patient 3, and leukocyte infiltration in all cases, which could not be attributed to disease progression. Conclusions: Allogeneic white cell immunotherapy (AWIT) from young, healthy donors is well tolerated with minimal side effects and shows antitumor activity against advanced-stage solid tumors. AWIT represents a novel, safe, and cost-effective immunotherapy that can be administered in an outpatient cancer clinic. |
| first_indexed | 2024-12-21T17:53:06Z |
| format | Article |
| id | doaj.art-78d3c2cfa10547e4bcc0a790ebb5fc13 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-12-21T17:53:06Z |
| publishDate | 2017-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-78d3c2cfa10547e4bcc0a790ebb5fc132022-12-21T18:55:17ZengElsevierHeliyon2405-84402017-10-01310e00438Young donor white blood cell immunotherapy induces extensive tumor necrosis in advanced-stage solid tumorsDipnarine Maharaj0Pedro G. Vianna1Wendy Ward2Anthony J. Messina3Trevor Rayborn4Jacqueline V. Gouvea5Richard D. Hammer6Zheng Cui7South Florida Bone Marrow Stem Cell Transplant Institute, Boynton Beach, Florida 33437, USA; Corresponding author.South Florida Bone Marrow Stem Cell Transplant Institute, Boynton Beach, Florida 33437, USA; Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USASouth Florida Bone Marrow Stem Cell Transplant Institute, Boynton Beach, Florida 33437, USASouth Florida Bone Marrow Stem Cell Transplant Institute, Boynton Beach, Florida 33437, USASouth Florida Bone Marrow Stem Cell Transplant Institute, Boynton Beach, Florida 33437, USASouth Florida Bone Marrow Stem Cell Transplant Institute, Boynton Beach, Florida 33437, USADepartment of Pathology, University of Missouri School of Medicine, Columbia, Missouri 65212, USADepartment of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USABackground: In the past decade, a variety of immunotherapy approaches focused predominantly on the adaptive immune system have shown unprecedented responses in patients with advanced-stage malignancies. However, studies in spontaneous regression/complete resistance (SR/CR) mice and humans have shown a novel innate cancer-killing activity mediated by granulocytes, which is completely transferable for prevention or therapy against established malignancies. Methods: Three patients with advanced, relapsed or refractory solid tumors for which no standard therapy was available or was refused were enrolled into this ongoing combined phase I/II open label clinical trial testing the safety, dose tolerance, and possible antineoplastic efficacy of sequential infusions of HLA-mismatched non-irradiated allogeneic white cells (68–91% granulocytes) collected by leukapheresis from young, healthy donors (age 18–35) following mobilization with granulocyte colony stimulating factor (G-CSF) and dexamethasone. Results: Besides fevers and flushing, no infusional toxicities were observed. All patients remained clinically stable following infusions with mild cytokine release syndrome and no evidence of transfusion-associated graft-versus-host disease, acute tumor lysis syndrome,or transfusion-associated acute lung injury. Pathological examination of all cases post-mortem revealed extensive tumor necrosis up to 80% in patients 1–2, 40–50% in patient 3, and leukocyte infiltration in all cases, which could not be attributed to disease progression. Conclusions: Allogeneic white cell immunotherapy (AWIT) from young, healthy donors is well tolerated with minimal side effects and shows antitumor activity against advanced-stage solid tumors. AWIT represents a novel, safe, and cost-effective immunotherapy that can be administered in an outpatient cancer clinic.http://www.sciencedirect.com/science/article/pii/S2405844017316936Health sciencesMedicineInternal medicineEvidence-based medicineOncologypharmaceutical science |
| spellingShingle | Dipnarine Maharaj Pedro G. Vianna Wendy Ward Anthony J. Messina Trevor Rayborn Jacqueline V. Gouvea Richard D. Hammer Zheng Cui Young donor white blood cell immunotherapy induces extensive tumor necrosis in advanced-stage solid tumors Heliyon Health sciences Medicine Internal medicine Evidence-based medicine Oncology pharmaceutical science |
| title | Young donor white blood cell immunotherapy induces extensive tumor necrosis in advanced-stage solid tumors |
| title_full | Young donor white blood cell immunotherapy induces extensive tumor necrosis in advanced-stage solid tumors |
| title_fullStr | Young donor white blood cell immunotherapy induces extensive tumor necrosis in advanced-stage solid tumors |
| title_full_unstemmed | Young donor white blood cell immunotherapy induces extensive tumor necrosis in advanced-stage solid tumors |
| title_short | Young donor white blood cell immunotherapy induces extensive tumor necrosis in advanced-stage solid tumors |
| title_sort | young donor white blood cell immunotherapy induces extensive tumor necrosis in advanced stage solid tumors |
| topic | Health sciences Medicine Internal medicine Evidence-based medicine Oncology pharmaceutical science |
| url | http://www.sciencedirect.com/science/article/pii/S2405844017316936 |
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