Anti‐CLL1‐based CAR T‐cells with 4‐1‐BB or CD28/CD27 stimulatory domains in treating childhood refractory/relapsed acute myeloid leukemia

Background Though the efficacy of anti C‐type lectin‐like molecule‐1 (CLL1) CAR T‐cells in refractory/relapsed acute myeloid leukemia (R/R‐AML) have been occasionally reported, the influence of co‐stimulatory domain CAR T‐cells is not investigated so far. Method Seven R/R‐AML children treated with a...

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Published inCancer medicine (Malden, MA) Vol. 12; no. 8; pp. 9655 - 9661
Main Authors Pei, Kunlin, Xu, Haoyu, Wang, Pengfei, Gan, Wening, Hu, Zhengbin, Su, Xiaoling, Zhang, Hui, He, Yingyi
Format Journal Article
LanguageEnglish
Published United States John Wiley & Sons, Inc 01.04.2023
John Wiley and Sons Inc
Wiley
Subjects
4‐1‐BB
Acute myeloid leukemia
Antigens
anti‐CLL1 CAR T cells
Brief Communication
CD27 antigen
CD28 antigen
CD28 Antigens
CD28/CD27
Chemotherapy
Child
Childhood
Children
Cytokines
Drug resistance
Graft versus host disease
Humans
Immunotherapy, Adoptive - adverse effects
Infections
Leukemia
Leukemia, Myeloid, Acute - therapy
Lymphocytes T
Myeloproliferative Disorders
Neurotoxicity
Patients
Pediatrics
refractory/relapsed
T-Lymphocytes
Transplants & implants
Viral infections
4-1-BB
refractory/relapsed
anti-CLL1 CAR T cells
CD28/CD27
acute myeloid leukemia
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Abstract Background Though the efficacy of anti C‐type lectin‐like molecule‐1 (CLL1) CAR T‐cells in refractory/relapsed acute myeloid leukemia (R/R‐AML) have been occasionally reported, the influence of co‐stimulatory domain CAR T‐cells is not investigated so far. Method Seven R/R‐AML children treated with anti‐CLL1 CAR T‐cells were enrolled onto this preliminary comparison study. Among these seven patients, four received CD28/CD27‐based CAR T‐cells therapy, and three received 4‐1BB‐based CAR T‐cells therapy. Result The overall response rates were 75% and 66.7% in CD28/CD27 and 4‐1BB group respectively. All patients experienced grade 1 to 2 cytokine release syndrome, with only one patient experiencing grade 2 immune effector cell‐associated neurotoxicity syndrome. The maximum CAR T‐cells durations were 156 and 274 days for CD28/CD27 group and 4‐1BB group respectively. The 1‐yr overall survival rate was 57.1%. Conclusions A preliminary similar efficacy/safety index was observed in anti‐CLL1‐based CAR T‐cells with 4‐1BB or CD28/CD27 co‐stimulatory elements in treating pediatric R/R‐AML. This preliminary report demonstrates that CD28/CD27‐ and 4‐1‐BB‐equipped CAR T‐cells have comparable effectiveness and safety indices in treating children with relapsed/refractoryacute myeloid leukemia.
AbstractList Though the efficacy of anti C-type lectin-like molecule-1 (CLL1) CAR T-cells in refractory/relapsed acute myeloid leukemia (R/R-AML) have been occasionally reported, the influence of co-stimulatory domain CAR T-cells is not investigated so far. Seven R/R-AML children treated with anti-CLL1 CAR T-cells were enrolled onto this preliminary comparison study. Among these seven patients, four received CD28/CD27-based CAR T-cells therapy, and three received 4-1BB-based CAR T-cells therapy. The overall response rates were 75% and 66.7% in CD28/CD27 and 4-1BB group respectively. All patients experienced grade 1 to 2 cytokine release syndrome, with only one patient experiencing grade 2 immune effector cell-associated neurotoxicity syndrome. The maximum CAR T-cells durations were 156 and 274 days for CD28/CD27 group and 4-1BB group respectively. The 1-yr overall survival rate was 57.1%. A preliminary similar efficacy/safety index was observed in anti-CLL1-based CAR T-cells with 4-1BB or CD28/CD27 co-stimulatory elements in treating pediatric R/R-AML.
This preliminary report demonstrates that CD28/CD27‐ and 4‐1‐BB‐equipped CAR T‐cells have comparable effectiveness and safety indices in treating children with relapsed/refractoryacute myeloid leukemia.
Abstract Background Though the efficacy of anti C‐type lectin‐like molecule‐1 (CLL1) CAR T‐cells in refractory/relapsed acute myeloid leukemia (R/R‐AML) have been occasionally reported, the influence of co‐stimulatory domain CAR T‐cells is not investigated so far. Method Seven R/R‐AML children treated with anti‐CLL1 CAR T‐cells were enrolled onto this preliminary comparison study. Among these seven patients, four received CD28/CD27‐based CAR T‐cells therapy, and three received 4‐1BB‐based CAR T‐cells therapy. Result The overall response rates were 75% and 66.7% in CD28/CD27 and 4‐1BB group respectively. All patients experienced grade 1 to 2 cytokine release syndrome, with only one patient experiencing grade 2 immune effector cell‐associated neurotoxicity syndrome. The maximum CAR T‐cells durations were 156 and 274 days for CD28/CD27 group and 4‐1BB group respectively. The 1‐yr overall survival rate was 57.1%. Conclusions A preliminary similar efficacy/safety index was observed in anti‐CLL1‐based CAR T‐cells with 4‐1BB or CD28/CD27 co‐stimulatory elements in treating pediatric R/R‐AML.
Background Though the efficacy of anti C‐type lectin‐like molecule‐1 (CLL1) CAR T‐cells in refractory/relapsed acute myeloid leukemia (R/R‐AML) have been occasionally reported, the influence of co‐stimulatory domain CAR T‐cells is not investigated so far. Method Seven R/R‐AML children treated with anti‐CLL1 CAR T‐cells were enrolled onto this preliminary comparison study. Among these seven patients, four received CD28/CD27‐based CAR T‐cells therapy, and three received 4‐1BB‐based CAR T‐cells therapy. Result The overall response rates were 75% and 66.7% in CD28/CD27 and 4‐1BB group respectively. All patients experienced grade 1 to 2 cytokine release syndrome, with only one patient experiencing grade 2 immune effector cell‐associated neurotoxicity syndrome. The maximum CAR T‐cells durations were 156 and 274 days for CD28/CD27 group and 4‐1BB group respectively. The 1‐yr overall survival rate was 57.1%. Conclusions A preliminary similar efficacy/safety index was observed in anti‐CLL1‐based CAR T‐cells with 4‐1BB or CD28/CD27 co‐stimulatory elements in treating pediatric R/R‐AML. This preliminary report demonstrates that CD28/CD27‐ and 4‐1‐BB‐equipped CAR T‐cells have comparable effectiveness and safety indices in treating children with relapsed/refractoryacute myeloid leukemia.
BackgroundThough the efficacy of anti C-type lectin-like molecule-1 (CLL1) CAR T-cells in refractory/relapsed acute myeloid leukemia (R/R-AML) have been occasionally reported, the influence of co-stimulatory domain CAR T-cells is not investigated so far.MethodSeven R/R-AML children treated with anti-CLL1 CAR T-cells were enrolled onto this preliminary comparison study. Among these seven patients, four received CD28/CD27-based CAR T-cells therapy, and three received 4-1BB-based CAR T-cells therapy.ResultThe overall response rates were 75% and 66.7% in CD28/CD27 and 4-1BB group respectively. All patients experienced grade 1 to 2 cytokine release syndrome, with only one patient experiencing grade 2 immune effector cell-associated neurotoxicity syndrome. The maximum CAR T-cells durations were 156 and 274 days for CD28/CD27 group and 4-1BB group respectively. The 1-yr overall survival rate was 57.1%.ConclusionsA preliminary similar efficacy/safety index was observed in anti-CLL1-based CAR T-cells with 4-1BB or CD28/CD27 co-stimulatory elements in treating pediatric R/R-AML.
Though the efficacy of anti C-type lectin-like molecule-1 (CLL1) CAR T-cells in refractory/relapsed acute myeloid leukemia (R/R-AML) have been occasionally reported, the influence of co-stimulatory domain CAR T-cells is not investigated so far.BACKGROUNDThough the efficacy of anti C-type lectin-like molecule-1 (CLL1) CAR T-cells in refractory/relapsed acute myeloid leukemia (R/R-AML) have been occasionally reported, the influence of co-stimulatory domain CAR T-cells is not investigated so far.Seven R/R-AML children treated with anti-CLL1 CAR T-cells were enrolled onto this preliminary comparison study. Among these seven patients, four received CD28/CD27-based CAR T-cells therapy, and three received 4-1BB-based CAR T-cells therapy.METHODSeven R/R-AML children treated with anti-CLL1 CAR T-cells were enrolled onto this preliminary comparison study. Among these seven patients, four received CD28/CD27-based CAR T-cells therapy, and three received 4-1BB-based CAR T-cells therapy.The overall response rates were 75% and 66.7% in CD28/CD27 and 4-1BB group respectively. All patients experienced grade 1 to 2 cytokine release syndrome, with only one patient experiencing grade 2 immune effector cell-associated neurotoxicity syndrome. The maximum CAR T-cells durations were 156 and 274 days for CD28/CD27 group and 4-1BB group respectively. The 1-yr overall survival rate was 57.1%.RESULTThe overall response rates were 75% and 66.7% in CD28/CD27 and 4-1BB group respectively. All patients experienced grade 1 to 2 cytokine release syndrome, with only one patient experiencing grade 2 immune effector cell-associated neurotoxicity syndrome. The maximum CAR T-cells durations were 156 and 274 days for CD28/CD27 group and 4-1BB group respectively. The 1-yr overall survival rate was 57.1%.A preliminary similar efficacy/safety index was observed in anti-CLL1-based CAR T-cells with 4-1BB or CD28/CD27 co-stimulatory elements in treating pediatric R/R-AML.CONCLUSIONSA preliminary similar efficacy/safety index was observed in anti-CLL1-based CAR T-cells with 4-1BB or CD28/CD27 co-stimulatory elements in treating pediatric R/R-AML.
Author Xu, Haoyu
Zhang, Hui
Gan, Wening
He, Yingyi
Pei, Kunlin
Hu, Zhengbin
Su, Xiaoling
Wang, Pengfei
AuthorAffiliation 2 Guangzhou Medical University Guangzhou 511495 Guangdong China
1 Department of Hematology/Oncology, Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 Guangdong China
AuthorAffiliation_xml – name: 1 Department of Hematology/Oncology, Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 Guangdong China
– name: 2 Guangzhou Medical University Guangzhou 511495 Guangdong China
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/37031462$$D View this record in MEDLINE/PubMed
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Keywords 4-1-BB
refractory/relapsed
anti-CLL1 CAR T cells
CD28/CD27
acute myeloid leukemia
Language English
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This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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Notes Kunlin Pei, Haoyu Xu and Pengfei Wang equally contributed to this study.
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Snippet Background Though the efficacy of anti C‐type lectin‐like molecule‐1 (CLL1) CAR T‐cells in refractory/relapsed acute myeloid leukemia (R/R‐AML) have been...
Though the efficacy of anti C-type lectin-like molecule-1 (CLL1) CAR T-cells in refractory/relapsed acute myeloid leukemia (R/R-AML) have been occasionally...
BackgroundThough the efficacy of anti C-type lectin-like molecule-1 (CLL1) CAR T-cells in refractory/relapsed acute myeloid leukemia (R/R-AML) have been...
This preliminary report demonstrates that CD28/CD27‐ and 4‐1‐BB‐equipped CAR T‐cells have comparable effectiveness and safety indices in treating children with...
Abstract Background Though the efficacy of anti C‐type lectin‐like molecule‐1 (CLL1) CAR T‐cells in refractory/relapsed acute myeloid leukemia (R/R‐AML) have...
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SubjectTerms 4‐1‐BB
Acute myeloid leukemia
Antigens
anti‐CLL1 CAR T cells
Brief Communication
CD27 antigen
CD28 antigen
CD28 Antigens
CD28/CD27
Chemotherapy
Child
Childhood
Children
Cytokines
Drug resistance
Graft versus host disease
Humans
Immunotherapy, Adoptive - adverse effects
Infections
Leukemia
Leukemia, Myeloid, Acute - therapy
Lymphocytes T
Myeloproliferative Disorders
Neurotoxicity
Patients
Pediatrics
refractory/relapsed
T-Lymphocytes
Transplants & implants
Viral infections
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Title Anti‐CLL1‐based CAR T‐cells with 4‐1‐BB or CD28/CD27 stimulatory domains in treating childhood refractory/relapsed acute myeloid leukemia
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fcam4.5916
https://www.ncbi.nlm.nih.gov/pubmed/37031462
https://www.proquest.com/docview/2811071697
https://www.proquest.com/docview/2799172873
https://pubmed.ncbi.nlm.nih.gov/PMC10166968
https://doaj.org/article/5768462a857c43be8290efd47cf8b70b
Volume 12
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