Combining AFM13, a Bispecific CD30/CD16 Antibody, with Cytokine-Activated Blood and Cord Blood-Derived NK Cells Facilitates CAR-like Responses Against CD30+ Malignancies.
| Title: | Combining AFM13, a Bispecific CD30/CD16 Antibody, with Cytokine-Activated Blood and Cord Blood-Derived NK Cells Facilitates CAR-like Responses Against CD30+ Malignancies. |
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| Authors: | Kerbauy LN; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Departments of Stem Cell Transplantation and Hemotherapy/Cellular Therapy, Hospital Israelita Albert Einstein, Sao Paulo, Brazil.; Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo (USP), Sao Paulo, Brazil.; Marin ND; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.; Kaplan M; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Banerjee PP; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Berrien-Elliott MM; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.; Becker-Hapak M; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.; Basar R; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Foster M; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.; Garcia Melo L; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Neal CC; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.; McClain E; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.; Daher M; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Nunez Cortes AK; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Desai S; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.; Inng Lim FW; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Mendt MC; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Schappe T; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.; Li L; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Shaim H; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Shanley M; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Ensley EL; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Uprety N; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Wong P; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.; Liu E; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Ang SO; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Cai R; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Nandivada V; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Mohanty V; Department of Bioinformatics and Computational Biology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.; Miao Q; Department of Bioinformatics and Computational Biology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.; Shen Y; Department of Bioinformatics and Computational Biology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.; Baran N; Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, Texas.; Fowlkes NW; Department of Veterinary Medicine and Surgery, The University of Texas, MD Anderson Cancer Center, Houston, Texas.; Chen K; Department of Bioinformatics and Computational Biology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.; Muniz-Feliciano L; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Champlin RE; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Nieto YL; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Koch J; Affimed GmbH, Heidelberg, Germany.; Treder M; Arjuna Therapeutics, Santiago de Compostela, Spain.; Fischer W; Affimed GmbH, Heidelberg, Germany.; Okamoto OK; Departments of Stem Cell Transplantation and Hemotherapy/Cellular Therapy, Hospital Israelita Albert Einstein, Sao Paulo, Brazil.; Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo (USP), Sao Paulo, Brazil.; Shpall EJ; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Fehniger TA; Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri. krezvani@mdanderson.org tfehnige@wustl.edu.; Rezvani K; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. krezvani@mdanderson.org tfehnige@wustl.edu. |
| Source: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2021 Jul 01; Vol. 27 (13), pp. 3744-3756. Date of Electronic Publication: 2021 May 13. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 9502500 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Denville, NJ : American Association for Cancer Research, c1995- |
| MeSH Terms: | Antibodies, Bispecific*/therapeutic use ; Immunotherapy*/methods ; Killer Cells, Natural*/immunology ; Leukemia*/therapy ; Lymphoma*/therapy; Blood/drug effects ; Blood/immunology ; Cytokines/pharmacology ; Fetal Blood/drug effects ; Fetal Blood/immunology ; Ki-1 Antigen/immunology ; Receptors, IgG/immunology ; Humans ; Cells, Cultured ; Combined Modality Therapy |
| Abstract: | Purpose: Natural killer (NK)-cell recognition and function against NK-resistant cancers remain substantial barriers to the broad application of NK-cell immunotherapy. Potential solutions include bispecific engagers that target NK-cell activity via an NK-activating receptor when simultaneously targeting a tumor-specific antigen, as well as enhancing functionality using IL12/15/18 cytokine pre-activation.; Experimental Design: We assessed single-cell NK-cell responses stimulated by the tetravalent bispecific antibody AFM13 that binds CD30 on leukemia/lymphoma targets and CD16A on various types of NK cells using mass cytometry and cytotoxicity assays. The combination of AFM13 and IL12/15/18 pre-activation of blood and cord blood-derived NK cells was investigated in vitro and in vivo.; Results: We found heterogeneity within AFM13-directed conventional blood NK cell (cNK) responses, as well as consistent AFM13-directed polyfunctional activation of mature NK cells across donors. NK-cell source also impacted the AFM13 response, with cNK cells from healthy donors exhibiting superior responses to those from patients with Hodgkin lymphoma. IL12/15/18-induced memory-like NK cells from peripheral blood exhibited enhanced killing of CD30+ lymphoma targets directed by AFM13, compared with cNK cells. Cord-blood NK cells preactivated with IL12/15/18 and ex vivo expanded with K562-based feeders also exhibited enhanced killing with AFM13 stimulation via upregulation of signaling pathways related to NK-cell effector function. AFM13-NK complex cells exhibited enhanced responses to CD30+ lymphomas in vitro and in vivo.; Conclusions: We identify AFM13 as a promising combination with cytokine-activated adult blood or cord-blood NK cells to treat CD30+ hematologic malignancies, warranting clinical trials with these novel combinations.; (©2021 American Association for Cancer Research.) |
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| Grant Information: | P30 CA016672 United States CA NCI NIH HHS; P50 CA100632 United States CA NCI NIH HHS; P50 CA171963 United States CA NCI NIH HHS; K12 CA167540 United States CA NCI NIH HHS; R01 CA205239 United States CA NCI NIH HHS; P30 CA091842 United States CA NCI NIH HHS; R01 CA211044 United States CA NCI NIH HHS; P01 CA148600 United States CA NCI NIH HHS |
| Substance Nomenclature: | 0 (Antibodies, Bispecific); 0 (Cytokines); 0 (Ki-1 Antigen); 0 (Receptors, IgG); 0 (AFM13) |
| Entry Date(s): | Date Created: 20210514 Date Completed: 20220402 Latest Revision: 20240923 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8254785 |
| DOI: | 10.1158/1078-0432.CCR-21-0164 |
| PMID: | 33986022 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't