A novel oral metronomic chemotherapy provokes tumor specific immunity resulting in colon cancer eradication in combination with anti-PD-1 therapy
In this study, we investigated the immune-modulating effects of a novel metronomic chemotherapy (MCT) featuring combined oral oxaliplatin (OXA) and pemetrexed (PMX) for colon cancer. OXA and PMX were ionically complexed with lysine derivative of deoxycholic acid (DCK), and incorporated into nanoemul...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Maharjan, Ruby [verfasserIn] Choi, Jeong Uk [verfasserIn] Kweon, Seho [verfasserIn] Pangeni, Rudra [verfasserIn] Lee, Na Kyeong [verfasserIn] Park, Seong Jin [verfasserIn] Chang, Kwan-Young [verfasserIn] Park, Jin Woo [verfasserIn] Byun, Youngro [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2022 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Biomaterials - Amsterdam [u.a.] : Elsevier Science, 1980, 281 |
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| Übergeordnetes Werk: |
volume:281 |
| DOI / URN: |
10.1016/j.biomaterials.2021.121334 |
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| 245 | 1 | 0 | |a A novel oral metronomic chemotherapy provokes tumor specific immunity resulting in colon cancer eradication in combination with anti-PD-1 therapy |
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| 520 | |a In this study, we investigated the immune-modulating effects of a novel metronomic chemotherapy (MCT) featuring combined oral oxaliplatin (OXA) and pemetrexed (PMX) for colon cancer. OXA and PMX were ionically complexed with lysine derivative of deoxycholic acid (DCK), and incorporated into nanoemulsions or colloidal dispersions, yielding OXA/DCK-NE and PMX/DCK-OP, respectively, to improve their oral bioavailabilities. MCT was not associated with significant lymphotoxicity whereas the maximum tolerated dose (MTD) afforded systemic immunosuppression. MCT was associated with more immunogenic cell death and tumor cell MHC-class I expression than was MTD. MCT improved the tumor antigen presentation of dendritic cells and increased the number of functional T cells in the tumor. MCT also helped to enhance antigen-specific memory responses both locally and systemically. By combining MCT with anti-programmed cell death protein-1 (αPD-1) therapy, the tumor volume was suppressed by 97.85 ± 84.88% compared to the control, resulting in a 95% complete response rate. Upon re-challenge, all tumor-free mice rejected secondary tumors, indicating the induction of a tumor specific memory response. Thus, MCT using an OXA and PMX combination, together with αPD-1, successfully treated colon cancer by activating both innate and adaptive immune cells and elicited tumor-specific long-term immune memory while avoiding toxicity caused by MTD treatment. | ||
| 650 | 4 | |a Oral metronomic chemotherapy | |
| 650 | 4 | |a Tumor microenvironment | |
| 650 | 4 | |a Immune checkpoint blockade | |
| 650 | 4 | |a Complete response | |
| 650 | 4 | |a Immunogenic cell death | |
| 650 | 4 | |a Tumor-specific immune memory | |
| 700 | 1 | |a Choi, Jeong Uk |e verfasserin |0 (orcid)0000-0002-3168-7189 |4 aut | |
| 700 | 1 | |a Kweon, Seho |e verfasserin |0 (orcid)0000-0002-0851-7843 |4 aut | |
| 700 | 1 | |a Pangeni, Rudra |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Na Kyeong |e verfasserin |0 (orcid)0000-0002-6461-4445 |4 aut | |
| 700 | 1 | |a Park, Seong Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Kwan-Young |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Jin Woo |e verfasserin |4 aut | |
| 700 | 1 | |a Byun, Youngro |e verfasserin |0 (orcid)0000-0002-3863-2236 |4 aut | |
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10.1016/j.biomaterials.2021.121334 doi (DE-627)ELV00733110X (ELSEVIER)S0142-9612(21)00690-6 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 44.09 bkl Maharjan, Ruby verfasserin (orcid)0000-0001-8945-9456 aut A novel oral metronomic chemotherapy provokes tumor specific immunity resulting in colon cancer eradication in combination with anti-PD-1 therapy 2022 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier In this study, we investigated the immune-modulating effects of a novel metronomic chemotherapy (MCT) featuring combined oral oxaliplatin (OXA) and pemetrexed (PMX) for colon cancer. OXA and PMX were ionically complexed with lysine derivative of deoxycholic acid (DCK), and incorporated into nanoemulsions or colloidal dispersions, yielding OXA/DCK-NE and PMX/DCK-OP, respectively, to improve their oral bioavailabilities. MCT was not associated with significant lymphotoxicity whereas the maximum tolerated dose (MTD) afforded systemic immunosuppression. MCT was associated with more immunogenic cell death and tumor cell MHC-class I expression than was MTD. MCT improved the tumor antigen presentation of dendritic cells and increased the number of functional T cells in the tumor. MCT also helped to enhance antigen-specific memory responses both locally and systemically. By combining MCT with anti-programmed cell death protein-1 (αPD-1) therapy, the tumor volume was suppressed by 97.85 ± 84.88% compared to the control, resulting in a 95% complete response rate. Upon re-challenge, all tumor-free mice rejected secondary tumors, indicating the induction of a tumor specific memory response. Thus, MCT using an OXA and PMX combination, together with αPD-1, successfully treated colon cancer by activating both innate and adaptive immune cells and elicited tumor-specific long-term immune memory while avoiding toxicity caused by MTD treatment. Oral metronomic chemotherapy Tumor microenvironment Immune checkpoint blockade Complete response Immunogenic cell death Tumor-specific immune memory Choi, Jeong Uk verfasserin (orcid)0000-0002-3168-7189 aut Kweon, Seho verfasserin (orcid)0000-0002-0851-7843 aut Pangeni, Rudra verfasserin aut Lee, Na Kyeong verfasserin (orcid)0000-0002-6461-4445 aut Park, Seong Jin verfasserin aut Chang, Kwan-Young verfasserin aut Park, Jin Woo verfasserin aut Byun, Youngro verfasserin (orcid)0000-0002-3863-2236 aut Enthalten in Biomaterials Amsterdam [u.a.] : Elsevier Science, 1980 281 Online-Ressource (DE-627)32043320X (DE-600)2004010-6 (DE-576)098614932 0142-9612 nnns volume:281 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.09 Medizintechnik AR 281 |
| spelling |
10.1016/j.biomaterials.2021.121334 doi (DE-627)ELV00733110X (ELSEVIER)S0142-9612(21)00690-6 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 44.09 bkl Maharjan, Ruby verfasserin (orcid)0000-0001-8945-9456 aut A novel oral metronomic chemotherapy provokes tumor specific immunity resulting in colon cancer eradication in combination with anti-PD-1 therapy 2022 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier In this study, we investigated the immune-modulating effects of a novel metronomic chemotherapy (MCT) featuring combined oral oxaliplatin (OXA) and pemetrexed (PMX) for colon cancer. OXA and PMX were ionically complexed with lysine derivative of deoxycholic acid (DCK), and incorporated into nanoemulsions or colloidal dispersions, yielding OXA/DCK-NE and PMX/DCK-OP, respectively, to improve their oral bioavailabilities. MCT was not associated with significant lymphotoxicity whereas the maximum tolerated dose (MTD) afforded systemic immunosuppression. MCT was associated with more immunogenic cell death and tumor cell MHC-class I expression than was MTD. MCT improved the tumor antigen presentation of dendritic cells and increased the number of functional T cells in the tumor. MCT also helped to enhance antigen-specific memory responses both locally and systemically. By combining MCT with anti-programmed cell death protein-1 (αPD-1) therapy, the tumor volume was suppressed by 97.85 ± 84.88% compared to the control, resulting in a 95% complete response rate. Upon re-challenge, all tumor-free mice rejected secondary tumors, indicating the induction of a tumor specific memory response. Thus, MCT using an OXA and PMX combination, together with αPD-1, successfully treated colon cancer by activating both innate and adaptive immune cells and elicited tumor-specific long-term immune memory while avoiding toxicity caused by MTD treatment. Oral metronomic chemotherapy Tumor microenvironment Immune checkpoint blockade Complete response Immunogenic cell death Tumor-specific immune memory Choi, Jeong Uk verfasserin (orcid)0000-0002-3168-7189 aut Kweon, Seho verfasserin (orcid)0000-0002-0851-7843 aut Pangeni, Rudra verfasserin aut Lee, Na Kyeong verfasserin (orcid)0000-0002-6461-4445 aut Park, Seong Jin verfasserin aut Chang, Kwan-Young verfasserin aut Park, Jin Woo verfasserin aut Byun, Youngro verfasserin (orcid)0000-0002-3863-2236 aut Enthalten in Biomaterials Amsterdam [u.a.] : Elsevier Science, 1980 281 Online-Ressource (DE-627)32043320X (DE-600)2004010-6 (DE-576)098614932 0142-9612 nnns volume:281 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.09 Medizintechnik AR 281 |
| allfields_unstemmed |
10.1016/j.biomaterials.2021.121334 doi (DE-627)ELV00733110X (ELSEVIER)S0142-9612(21)00690-6 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 44.09 bkl Maharjan, Ruby verfasserin (orcid)0000-0001-8945-9456 aut A novel oral metronomic chemotherapy provokes tumor specific immunity resulting in colon cancer eradication in combination with anti-PD-1 therapy 2022 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier In this study, we investigated the immune-modulating effects of a novel metronomic chemotherapy (MCT) featuring combined oral oxaliplatin (OXA) and pemetrexed (PMX) for colon cancer. OXA and PMX were ionically complexed with lysine derivative of deoxycholic acid (DCK), and incorporated into nanoemulsions or colloidal dispersions, yielding OXA/DCK-NE and PMX/DCK-OP, respectively, to improve their oral bioavailabilities. MCT was not associated with significant lymphotoxicity whereas the maximum tolerated dose (MTD) afforded systemic immunosuppression. MCT was associated with more immunogenic cell death and tumor cell MHC-class I expression than was MTD. MCT improved the tumor antigen presentation of dendritic cells and increased the number of functional T cells in the tumor. MCT also helped to enhance antigen-specific memory responses both locally and systemically. By combining MCT with anti-programmed cell death protein-1 (αPD-1) therapy, the tumor volume was suppressed by 97.85 ± 84.88% compared to the control, resulting in a 95% complete response rate. Upon re-challenge, all tumor-free mice rejected secondary tumors, indicating the induction of a tumor specific memory response. Thus, MCT using an OXA and PMX combination, together with αPD-1, successfully treated colon cancer by activating both innate and adaptive immune cells and elicited tumor-specific long-term immune memory while avoiding toxicity caused by MTD treatment. Oral metronomic chemotherapy Tumor microenvironment Immune checkpoint blockade Complete response Immunogenic cell death Tumor-specific immune memory Choi, Jeong Uk verfasserin (orcid)0000-0002-3168-7189 aut Kweon, Seho verfasserin (orcid)0000-0002-0851-7843 aut Pangeni, Rudra verfasserin aut Lee, Na Kyeong verfasserin (orcid)0000-0002-6461-4445 aut Park, Seong Jin verfasserin aut Chang, Kwan-Young verfasserin aut Park, Jin Woo verfasserin aut Byun, Youngro verfasserin (orcid)0000-0002-3863-2236 aut Enthalten in Biomaterials Amsterdam [u.a.] : Elsevier Science, 1980 281 Online-Ressource (DE-627)32043320X (DE-600)2004010-6 (DE-576)098614932 0142-9612 nnns volume:281 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.09 Medizintechnik AR 281 |
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10.1016/j.biomaterials.2021.121334 doi (DE-627)ELV00733110X (ELSEVIER)S0142-9612(21)00690-6 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 44.09 bkl Maharjan, Ruby verfasserin (orcid)0000-0001-8945-9456 aut A novel oral metronomic chemotherapy provokes tumor specific immunity resulting in colon cancer eradication in combination with anti-PD-1 therapy 2022 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier In this study, we investigated the immune-modulating effects of a novel metronomic chemotherapy (MCT) featuring combined oral oxaliplatin (OXA) and pemetrexed (PMX) for colon cancer. OXA and PMX were ionically complexed with lysine derivative of deoxycholic acid (DCK), and incorporated into nanoemulsions or colloidal dispersions, yielding OXA/DCK-NE and PMX/DCK-OP, respectively, to improve their oral bioavailabilities. MCT was not associated with significant lymphotoxicity whereas the maximum tolerated dose (MTD) afforded systemic immunosuppression. MCT was associated with more immunogenic cell death and tumor cell MHC-class I expression than was MTD. MCT improved the tumor antigen presentation of dendritic cells and increased the number of functional T cells in the tumor. MCT also helped to enhance antigen-specific memory responses both locally and systemically. By combining MCT with anti-programmed cell death protein-1 (αPD-1) therapy, the tumor volume was suppressed by 97.85 ± 84.88% compared to the control, resulting in a 95% complete response rate. Upon re-challenge, all tumor-free mice rejected secondary tumors, indicating the induction of a tumor specific memory response. Thus, MCT using an OXA and PMX combination, together with αPD-1, successfully treated colon cancer by activating both innate and adaptive immune cells and elicited tumor-specific long-term immune memory while avoiding toxicity caused by MTD treatment. Oral metronomic chemotherapy Tumor microenvironment Immune checkpoint blockade Complete response Immunogenic cell death Tumor-specific immune memory Choi, Jeong Uk verfasserin (orcid)0000-0002-3168-7189 aut Kweon, Seho verfasserin (orcid)0000-0002-0851-7843 aut Pangeni, Rudra verfasserin aut Lee, Na Kyeong verfasserin (orcid)0000-0002-6461-4445 aut Park, Seong Jin verfasserin aut Chang, Kwan-Young verfasserin aut Park, Jin Woo verfasserin aut Byun, Youngro verfasserin (orcid)0000-0002-3863-2236 aut Enthalten in Biomaterials Amsterdam [u.a.] : Elsevier Science, 1980 281 Online-Ressource (DE-627)32043320X (DE-600)2004010-6 (DE-576)098614932 0142-9612 nnns volume:281 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.09 Medizintechnik AR 281 |
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10.1016/j.biomaterials.2021.121334 doi (DE-627)ELV00733110X (ELSEVIER)S0142-9612(21)00690-6 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 44.09 bkl Maharjan, Ruby verfasserin (orcid)0000-0001-8945-9456 aut A novel oral metronomic chemotherapy provokes tumor specific immunity resulting in colon cancer eradication in combination with anti-PD-1 therapy 2022 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier In this study, we investigated the immune-modulating effects of a novel metronomic chemotherapy (MCT) featuring combined oral oxaliplatin (OXA) and pemetrexed (PMX) for colon cancer. OXA and PMX were ionically complexed with lysine derivative of deoxycholic acid (DCK), and incorporated into nanoemulsions or colloidal dispersions, yielding OXA/DCK-NE and PMX/DCK-OP, respectively, to improve their oral bioavailabilities. MCT was not associated with significant lymphotoxicity whereas the maximum tolerated dose (MTD) afforded systemic immunosuppression. MCT was associated with more immunogenic cell death and tumor cell MHC-class I expression than was MTD. MCT improved the tumor antigen presentation of dendritic cells and increased the number of functional T cells in the tumor. MCT also helped to enhance antigen-specific memory responses both locally and systemically. By combining MCT with anti-programmed cell death protein-1 (αPD-1) therapy, the tumor volume was suppressed by 97.85 ± 84.88% compared to the control, resulting in a 95% complete response rate. Upon re-challenge, all tumor-free mice rejected secondary tumors, indicating the induction of a tumor specific memory response. Thus, MCT using an OXA and PMX combination, together with αPD-1, successfully treated colon cancer by activating both innate and adaptive immune cells and elicited tumor-specific long-term immune memory while avoiding toxicity caused by MTD treatment. Oral metronomic chemotherapy Tumor microenvironment Immune checkpoint blockade Complete response Immunogenic cell death Tumor-specific immune memory Choi, Jeong Uk verfasserin (orcid)0000-0002-3168-7189 aut Kweon, Seho verfasserin (orcid)0000-0002-0851-7843 aut Pangeni, Rudra verfasserin aut Lee, Na Kyeong verfasserin (orcid)0000-0002-6461-4445 aut Park, Seong Jin verfasserin aut Chang, Kwan-Young verfasserin aut Park, Jin Woo verfasserin aut Byun, Youngro verfasserin (orcid)0000-0002-3863-2236 aut Enthalten in Biomaterials Amsterdam [u.a.] : Elsevier Science, 1980 281 Online-Ressource (DE-627)32043320X (DE-600)2004010-6 (DE-576)098614932 0142-9612 nnns volume:281 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.09 Medizintechnik AR 281 |
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Maharjan, Ruby @@aut@@ Choi, Jeong Uk @@aut@@ Kweon, Seho @@aut@@ Pangeni, Rudra @@aut@@ Lee, Na Kyeong @@aut@@ Park, Seong Jin @@aut@@ Chang, Kwan-Young @@aut@@ Park, Jin Woo @@aut@@ Byun, Youngro @@aut@@ |
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Maharjan, Ruby |
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Maharjan, Ruby ddc 570 fid BIODIV bkl 44.09 misc Oral metronomic chemotherapy misc Tumor microenvironment misc Immune checkpoint blockade misc Complete response misc Immunogenic cell death misc Tumor-specific immune memory A novel oral metronomic chemotherapy provokes tumor specific immunity resulting in colon cancer eradication in combination with anti-PD-1 therapy |
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570 DE-600 BIODIV DE-30 fid 44.09 bkl A novel oral metronomic chemotherapy provokes tumor specific immunity resulting in colon cancer eradication in combination with anti-PD-1 therapy Oral metronomic chemotherapy Tumor microenvironment Immune checkpoint blockade Complete response Immunogenic cell death Tumor-specific immune memory |
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ddc 570 fid BIODIV bkl 44.09 misc Oral metronomic chemotherapy misc Tumor microenvironment misc Immune checkpoint blockade misc Complete response misc Immunogenic cell death misc Tumor-specific immune memory |
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a novel oral metronomic chemotherapy provokes tumor specific immunity resulting in colon cancer eradication in combination with anti-pd-1 therapy |
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A novel oral metronomic chemotherapy provokes tumor specific immunity resulting in colon cancer eradication in combination with anti-PD-1 therapy |
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In this study, we investigated the immune-modulating effects of a novel metronomic chemotherapy (MCT) featuring combined oral oxaliplatin (OXA) and pemetrexed (PMX) for colon cancer. OXA and PMX were ionically complexed with lysine derivative of deoxycholic acid (DCK), and incorporated into nanoemulsions or colloidal dispersions, yielding OXA/DCK-NE and PMX/DCK-OP, respectively, to improve their oral bioavailabilities. MCT was not associated with significant lymphotoxicity whereas the maximum tolerated dose (MTD) afforded systemic immunosuppression. MCT was associated with more immunogenic cell death and tumor cell MHC-class I expression than was MTD. MCT improved the tumor antigen presentation of dendritic cells and increased the number of functional T cells in the tumor. MCT also helped to enhance antigen-specific memory responses both locally and systemically. By combining MCT with anti-programmed cell death protein-1 (αPD-1) therapy, the tumor volume was suppressed by 97.85 ± 84.88% compared to the control, resulting in a 95% complete response rate. Upon re-challenge, all tumor-free mice rejected secondary tumors, indicating the induction of a tumor specific memory response. Thus, MCT using an OXA and PMX combination, together with αPD-1, successfully treated colon cancer by activating both innate and adaptive immune cells and elicited tumor-specific long-term immune memory while avoiding toxicity caused by MTD treatment. |
| abstractGer |
In this study, we investigated the immune-modulating effects of a novel metronomic chemotherapy (MCT) featuring combined oral oxaliplatin (OXA) and pemetrexed (PMX) for colon cancer. OXA and PMX were ionically complexed with lysine derivative of deoxycholic acid (DCK), and incorporated into nanoemulsions or colloidal dispersions, yielding OXA/DCK-NE and PMX/DCK-OP, respectively, to improve their oral bioavailabilities. MCT was not associated with significant lymphotoxicity whereas the maximum tolerated dose (MTD) afforded systemic immunosuppression. MCT was associated with more immunogenic cell death and tumor cell MHC-class I expression than was MTD. MCT improved the tumor antigen presentation of dendritic cells and increased the number of functional T cells in the tumor. MCT also helped to enhance antigen-specific memory responses both locally and systemically. By combining MCT with anti-programmed cell death protein-1 (αPD-1) therapy, the tumor volume was suppressed by 97.85 ± 84.88% compared to the control, resulting in a 95% complete response rate. Upon re-challenge, all tumor-free mice rejected secondary tumors, indicating the induction of a tumor specific memory response. Thus, MCT using an OXA and PMX combination, together with αPD-1, successfully treated colon cancer by activating both innate and adaptive immune cells and elicited tumor-specific long-term immune memory while avoiding toxicity caused by MTD treatment. |
| abstract_unstemmed |
In this study, we investigated the immune-modulating effects of a novel metronomic chemotherapy (MCT) featuring combined oral oxaliplatin (OXA) and pemetrexed (PMX) for colon cancer. OXA and PMX were ionically complexed with lysine derivative of deoxycholic acid (DCK), and incorporated into nanoemulsions or colloidal dispersions, yielding OXA/DCK-NE and PMX/DCK-OP, respectively, to improve their oral bioavailabilities. MCT was not associated with significant lymphotoxicity whereas the maximum tolerated dose (MTD) afforded systemic immunosuppression. MCT was associated with more immunogenic cell death and tumor cell MHC-class I expression than was MTD. MCT improved the tumor antigen presentation of dendritic cells and increased the number of functional T cells in the tumor. MCT also helped to enhance antigen-specific memory responses both locally and systemically. By combining MCT with anti-programmed cell death protein-1 (αPD-1) therapy, the tumor volume was suppressed by 97.85 ± 84.88% compared to the control, resulting in a 95% complete response rate. Upon re-challenge, all tumor-free mice rejected secondary tumors, indicating the induction of a tumor specific memory response. Thus, MCT using an OXA and PMX combination, together with αPD-1, successfully treated colon cancer by activating both innate and adaptive immune cells and elicited tumor-specific long-term immune memory while avoiding toxicity caused by MTD treatment. |
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| score |
7.399349 |