Inhibition of the CD47-SIRPα axis for cancer therapy: A systematic review and meta-analysis of emerging clinical data
CD47-SIRPα interaction acts as a “don’t eat me” signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systemat...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1027235/full |
| _version_ | 1798019031397040128 |
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| author | Ji Son Rodney Cheng-En Hsieh Rodney Cheng-En Hsieh Heather Y. Lin Kate J. Krause Ying Yuan Amadeo B. Biter James Welsh Michael A. Curran David S. Hong |
| author_facet | Ji Son Rodney Cheng-En Hsieh Rodney Cheng-En Hsieh Heather Y. Lin Kate J. Krause Ying Yuan Amadeo B. Biter James Welsh Michael A. Curran David S. Hong |
| author_sort | Ji Son |
| collection | DOAJ |
| description | CD47-SIRPα interaction acts as a “don’t eat me” signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systematic review and meta-analysis of relevant databases and conference abstracts including clinical trials using CD47 and/or SIRPα inhibitors in cancer treatment. Nonlinear mixed models were applied for comparison of response and toxicity. We retrieved 317 articles, 24 of which were eligible. These included 771 response-evaluable patients with hematologic (47.1%) and solid tumors (52.9%). Of these, 6.4% experienced complete response, 10.4% partial response, and 26.1% stable disease for a 16.7% objective response rate (ORR), 42.8% disease control rate, and 4.8-month median duration of response. ORR was significantly higher for hematologic cancers (25.3%) than solid cancers (9.1%, p=0.042). Comparing by mechanism, seven CD47 monoclonal antibodies (mAbs) and six selective SIRPα blockers were given alone or combined with checkpoint inhibitors, targeted therapy, and/or chemotherapy. In solid cancers, selective SIRPα blockade showed a higher ORR (16.2%) than anti-CD47 mAbs (2.8%, p=0.079), which was significant for combination therapies (ORR 28.3% vs 3.0%, respectively, p=0.010). Responses were seen in head and neck, colorectal, endometrial, ovarian, hepatocellular, non-small cell lung, and HER2+gastroesophageal cancers. Dose-limiting toxicity (DLT) was seen in 3.3% of patients (5.4% anti-CD47 mAbs, 1.4% selective SIRPα blockers; p=0.01). The frequency of treatment-related adverse events (TRAEs) ≥grade 3 was 18.0%, similar between the two groups (p=0.082), and mostly laboratory abnormalities. For anti-CD47 mAbs, the most common toxicities included grade 1-2 fatigue (27.2%), headache (21.0%), and anemia (20.5%). For selective SIRPα blockers, these included grade 1-2 infusion reaction (23.1%) and fatigue (15.8%). Anti-CD47 mAbs were significantly more likely than selective SIRPα blockers to cause grade 1-2 fever, chills, nausea/vomiting, headache, and anemia. In conclusion, combination therapies using selective SIRPα blockade had higher response rates in solid tumors than anti-CD47 mAb combinations. Hematologic changes were the main TRAEs, and selective SIRPα blockers seemed to have a better grade 1-2 toxicity profile. Treatment was well-tolerated with minimal DLTs. |
| first_indexed | 2024-04-11T16:34:06Z |
| format | Article |
| id | doaj.art-b039dd1c5c03422caa8414a4fe15bc04 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T16:34:06Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-b039dd1c5c03422caa8414a4fe15bc042022-12-22T04:13:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10272351027235Inhibition of the CD47-SIRPα axis for cancer therapy: A systematic review and meta-analysis of emerging clinical dataJi Son0Rodney Cheng-En Hsieh1Rodney Cheng-En Hsieh2Heather Y. Lin3Kate J. Krause4Ying Yuan5Amadeo B. Biter6James Welsh7Michael A. Curran8David S. Hong9Departments of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartments of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Radiation Oncology, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan, TaiwanDepartments of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartments of Research Medical Library, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartments of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartments of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartments of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartments of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartments of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesCD47-SIRPα interaction acts as a “don’t eat me” signal and is exploited by cancer to downregulate innate and adaptive immune surveillance. There has been intense interest to develop a mechanism of blockade, and we aimed to analyze the emerging data from early clinical trials. We performed a systematic review and meta-analysis of relevant databases and conference abstracts including clinical trials using CD47 and/or SIRPα inhibitors in cancer treatment. Nonlinear mixed models were applied for comparison of response and toxicity. We retrieved 317 articles, 24 of which were eligible. These included 771 response-evaluable patients with hematologic (47.1%) and solid tumors (52.9%). Of these, 6.4% experienced complete response, 10.4% partial response, and 26.1% stable disease for a 16.7% objective response rate (ORR), 42.8% disease control rate, and 4.8-month median duration of response. ORR was significantly higher for hematologic cancers (25.3%) than solid cancers (9.1%, p=0.042). Comparing by mechanism, seven CD47 monoclonal antibodies (mAbs) and six selective SIRPα blockers were given alone or combined with checkpoint inhibitors, targeted therapy, and/or chemotherapy. In solid cancers, selective SIRPα blockade showed a higher ORR (16.2%) than anti-CD47 mAbs (2.8%, p=0.079), which was significant for combination therapies (ORR 28.3% vs 3.0%, respectively, p=0.010). Responses were seen in head and neck, colorectal, endometrial, ovarian, hepatocellular, non-small cell lung, and HER2+gastroesophageal cancers. Dose-limiting toxicity (DLT) was seen in 3.3% of patients (5.4% anti-CD47 mAbs, 1.4% selective SIRPα blockers; p=0.01). The frequency of treatment-related adverse events (TRAEs) ≥grade 3 was 18.0%, similar between the two groups (p=0.082), and mostly laboratory abnormalities. For anti-CD47 mAbs, the most common toxicities included grade 1-2 fatigue (27.2%), headache (21.0%), and anemia (20.5%). For selective SIRPα blockers, these included grade 1-2 infusion reaction (23.1%) and fatigue (15.8%). Anti-CD47 mAbs were significantly more likely than selective SIRPα blockers to cause grade 1-2 fever, chills, nausea/vomiting, headache, and anemia. In conclusion, combination therapies using selective SIRPα blockade had higher response rates in solid tumors than anti-CD47 mAb combinations. Hematologic changes were the main TRAEs, and selective SIRPα blockers seemed to have a better grade 1-2 toxicity profile. Treatment was well-tolerated with minimal DLTs.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1027235/fullCD47 inhibitorSIRPα inhibitornext generation checkpoint inhibitioncheckpoint inhibitor resistanceclinical trialnovel therapeutics |
| spellingShingle | Ji Son Rodney Cheng-En Hsieh Rodney Cheng-En Hsieh Heather Y. Lin Kate J. Krause Ying Yuan Amadeo B. Biter James Welsh Michael A. Curran David S. Hong Inhibition of the CD47-SIRPα axis for cancer therapy: A systematic review and meta-analysis of emerging clinical data Frontiers in Immunology CD47 inhibitor SIRPα inhibitor next generation checkpoint inhibition checkpoint inhibitor resistance clinical trial novel therapeutics |
| title | Inhibition of the CD47-SIRPα axis for cancer therapy: A systematic review and meta-analysis of emerging clinical data |
| title_full | Inhibition of the CD47-SIRPα axis for cancer therapy: A systematic review and meta-analysis of emerging clinical data |
| title_fullStr | Inhibition of the CD47-SIRPα axis for cancer therapy: A systematic review and meta-analysis of emerging clinical data |
| title_full_unstemmed | Inhibition of the CD47-SIRPα axis for cancer therapy: A systematic review and meta-analysis of emerging clinical data |
| title_short | Inhibition of the CD47-SIRPα axis for cancer therapy: A systematic review and meta-analysis of emerging clinical data |
| title_sort | inhibition of the cd47 sirpα axis for cancer therapy a systematic review and meta analysis of emerging clinical data |
| topic | CD47 inhibitor SIRPα inhibitor next generation checkpoint inhibition checkpoint inhibitor resistance clinical trial novel therapeutics |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1027235/full |
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