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Kerbauy LN, Marin ND, Kaplan M, et al. Combining AFM13, a Bispecific CD30/CD16 Antibody, with Cytokine-Activated Blood and Cord Blood-Derived NK Cells Facilitates CAR-like Responses Against CD30. Clin Cancer Res. 2021;27(13):3744-3756doi: 10.1158/1078-0432.CCR-21-0164.
Kerbauy, L. N., Marin, N. D., Kaplan, M., Banerjee, P. P., Berrien-Elliott, M. M., Becker-Hapak, M., Basar, R., Foster, M., Garcia Melo, L., Neal, C. C., McClain, E., Daher, M., Nunez Cortes, A. K., Desai, S., Inng Lim, F. W., Mendt, M. C., Schappe, T., Li, L., Shaim, H., Shanley, M., Ensley, E. L., Uprety, N., Wong, P., Liu, E., Ang, S. O., Cai, R., Nandivada, V., Mohanty, V., Miao, Q., Shen, Y., Baran, N., Fowlkes, N. W., Chen, K., Muniz-Feliciano, L., Champlin, R. E., Nieto, Y. L., Koch, J., Treder, M., Fischer, W., Okamoto, O. K., Shpall, E. J., Fehniger, T. A., & Rezvani, K. (2021). Combining AFM13, a Bispecific CD30/CD16 Antibody, with Cytokine-Activated Blood and Cord Blood-Derived NK Cells Facilitates CAR-like Responses Against CD30. Clinical cancer research : an official journal of the American Association for Cancer Research, 27(13), 3744-3756. https://doi.org/10.1158/1078-0432.CCR-21-0164
Kerbauy, Lucila N, et al. "Combining AFM13, a Bispecific CD30/CD16 Antibody, with Cytokine-Activated Blood and Cord Blood-Derived NK Cells Facilitates CAR-like Responses Against CD30." Clinical cancer research : an official journal of the American Association for Cancer Research vol. 27,13 (2021): 3744-3756. doi: https://doi.org/10.1158/1078-0432.CCR-21-0164
Kerbauy LN, Marin ND, Kaplan M, Banerjee PP, Berrien-Elliott MM, Becker-Hapak M, Basar R, Foster M, Garcia Melo L, Neal CC, McClain E, Daher M, Nunez Cortes AK, Desai S, Inng Lim FW, Mendt MC, Schappe T, Li L, Shaim H, Shanley M, Ensley EL, Uprety N, Wong P, Liu E, Ang SO, Cai R, Nandivada V, Mohanty V, Miao Q, Shen Y, Baran N, Fowlkes NW, Chen K, Muniz-Feliciano L, Champlin RE, Nieto YL, Koch J, Treder M, Fischer W, Okamoto OK, Shpall EJ, Fehniger TA, Rezvani K. Combining AFM13, a Bispecific CD30/CD16 Antibody, with Cytokine-Activated Blood and Cord Blood-Derived NK Cells Facilitates CAR-like Responses Against CD30. Clin Cancer Res. 2021 Jul 01;27(13):3744-3756. doi: 10.1158/1078-0432.CCR-21-0164. Epub 2021 May 13. PMID: 33986022; PMCID: PMC8254785.
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Clin Cancer Res. 2021 Jul 01;27(13):3744-3756. doi: 10.1158/1078-0432.CCR-21-0164. Epub 2021 May 13.

Combining AFM13, a Bispecific CD30/CD16 Antibody, with Cytokine-Activated Blood and Cord Blood-Derived NK Cells Facilitates CAR-like Responses Against CD30.

Clinical cancer research : an official journal of the American Association for Cancer Research

Lucila N Kerbauy, Nancy D Marin, Mecit Kaplan, Pinaki P Banerjee, Melissa M Berrien-Elliott, Michelle Becker-Hapak, Rafet Basar, Mark Foster, Luciana Garcia Melo, Carly C Neal, Ethan McClain, May Daher, Ana Karen Nunez Cortes, Sweta Desai, Francesca Wei Inng Lim, Mayela Carolina Mendt, Timothy Schappe, Li Li, Hila Shaim, Mayra Shanley, Emily L Ensley, Nadima Uprety, Pamela Wong, Enli Liu, Sonny O Ang, Rong Cai, Vandana Nandivada, Vakul Mohanty, Qi Miao, Yifei Shen, Natalia Baran, Natalie W Fowlkes, Ken Chen, Luis Muniz-Feliciano, Richard E Champlin, Yago L Nieto, Joachim Koch, Martin Treder, Wolfgang Fischer, Oswaldo Keith Okamoto, Elizabeth J Shpall, Todd A Fehniger, Katayoun Rezvani

Affiliations

  1. Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
  2. Departments of Stem Cell Transplantation and Hemotherapy/Cellular Therapy, Hospital Israelita Albert Einstein, Sao Paulo, Brazil.
  3. Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo (USP), Sao Paulo, Brazil.
  4. Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri.
  5. Department of Bioinformatics and Computational Biology, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
  6. Department of Leukemia, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
  7. Department of Veterinary Medicine and Surgery, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
  8. Affimed GmbH, Heidelberg, Germany.
  9. Arjuna Therapeutics, Santiago de Compostela, Spain.
  10. Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, Missouri. [email protected] [email protected].
  11. Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. [email protected] [email protected].

PMID: 33986022 PMCID: PMC8254785 DOI: 10.1158/1078-0432.CCR-21-0164

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

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

CONCLUSIONS: We identify AFM13 as a promising combination with cytokine-activated adult blood or cord-blood NK cells to treat CD30

©2021 American Association for Cancer Research.

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