Ying Qiu1, Mark M Yun2, Xuebin Dong3, Mingbao Xu4, Ruidong Zhao1, Xia Han1, Erxia Zhou1, Feiyu Yun1, Wuyun Su1, Caixia Liu1, Haiyan Zhao1, Xin Tong5, Jin Gao6, Xiaohui Ouyang1, Sheng Yun7. 1. Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China. 2. Heart of England National Health Service Foundation Trust, Bordesley Green, East Birmingham, UK. 3. Guy's and St Thomas' Hospital National Health Service Foundation Trust, London, UK. 4. Beijing Armed Police General Hospital, Beijing, China. 5. Second Hospital of Lanzhou University, Lanzhou, China. 6. Jing-Meng Stem Cell Company, Beijing, China. 7. Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China. Electronic address: sheng.yun@hotmail.co.uk.
Abstract
BACKGROUND AIMS: Refractory B-cell lymphomas are difficult to successfully treat with current chemotherapeutic regimens; however, immunotherapy may be an effective form of treatment for these patients. METHODS: Fourteen refractory lymphoma patients (age, 29-74 y) were enrolled in the trial. α-1,3-galactosyl (α-Gal) epitopes were synthesized on lymphoma cell membranes with the use of bovine recombinant α-1,3-galactosyltransferase (α-GT) and neuraminidase to enhance tumor immunogenicity. Subsequent incubation of processed cell membranes with autologous dendritic cells (DCs) in the presence of human serum containing abundant natural anti-α-Gal immunoglobulin G led to the effective phagocytosis of tumor membranes by DCs. The pulsed DCs and autologous cytokine-induced killer cells were then co-cultured to promote maximum cytotoxicity to lymphoma cells and were infused back into the donor lymphoma patients. Therapeutic responses were assessed by clinical observation, laboratory tests and a computed tomography scan at 6 months after treatment. RESULTS: Complete and partial remission occurred in four and three patients, respectively. The disease status remained unchanged in five patients, and disease progression was observed in two patients. No serious side effects or autoimmune diseases were observed in any participants. Serum lactate dehydrogenase and β2-macroglobulin decreased in 11 and 14 patients, respectively. All patients showed robust systemic cytotoxicity in response to tumor lysate as measured by interferon-γ expression in peripheral blood mononuclear cells after treatment (P < 0.001). The number of peripheral immune effector cells (CD3(+)/CD4(+), CD8(+)/CD28(+) and CD16(+)/CD56(+) cells) increased significantly (P < 0.05) 3 months after treatment. CONCLUSIONS: Lymphoma cell-specific α-Gal immunotherapy is safe, effective and has great potential for the treatment of refractory B-cell lymphoma.
BACKGROUND AIMS: Refractory B-cell lymphomas are difficult to successfully treat with current chemotherapeutic regimens; however, immunotherapy may be an effective form of treatment for these patients. METHODS: Fourteen refractory lymphomapatients (age, 29-74 y) were enrolled in the trial. α-1,3-galactosyl (α-Gal) epitopes were synthesized on lymphoma cell membranes with the use of bovine recombinant α-1,3-galactosyltransferase (α-GT) and neuraminidase to enhance tumor immunogenicity. Subsequent incubation of processed cell membranes with autologous dendritic cells (DCs) in the presence of human serum containing abundant natural anti-α-Gal immunoglobulin G led to the effective phagocytosis of tumor membranes by DCs. The pulsed DCs and autologous cytokine-induced killer cells were then co-cultured to promote maximum cytotoxicity to lymphoma cells and were infused back into the donorlymphomapatients. Therapeutic responses were assessed by clinical observation, laboratory tests and a computed tomography scan at 6 months after treatment. RESULTS: Complete and partial remission occurred in four and three patients, respectively. The disease status remained unchanged in five patients, and disease progression was observed in two patients. No serious side effects or autoimmune diseases were observed in any participants. Serum lactate dehydrogenase and β2-macroglobulin decreased in 11 and 14 patients, respectively. All patients showed robust systemic cytotoxicity in response to tumor lysate as measured by interferon-γ expression in peripheral blood mononuclear cells after treatment (P < 0.001). The number of peripheral immune effector cells (CD3(+)/CD4(+), CD8(+)/CD28(+) and CD16(+)/CD56(+) cells) increased significantly (P < 0.05) 3 months after treatment. CONCLUSIONS:Lymphoma cell-specific α-Gal immunotherapy is safe, effective and has great potential for the treatment of refractory B-cell lymphoma.
Authors: Alfredo Pherez-Farah; Rosa Del Carmen López-Sánchez; Luis Mario Villela-Martínez; Rocío Ortiz-López; Brady E Beltrán; José Ascención Hernández-Hernández Journal: Cancers (Basel) Date: 2022-04-19 Impact factor: 6.575