A preclinical study into a novel cellular therapy for lymphoma developed in the USA has shown promise, researchers have reported.
The treatment involves taking natural killer (NK) cells from donated umbilical cord blood, and activating them with cytokines. The cells are then stimulated to increase their numbers (expanded). These are then combined with AFM13 – an investigational bispecific antibody targeting CD16a and CD30.
The researchers from The University of Texas MD Anderson Cancer Center say their cellular treatment displayed strong anti-tumour activity against CD30+ lymphoma cells in laboratory experiments and in mice.
Senior author Professor Katy Rezvani said: “This preclinical work provided proof of principle for NK cells precomplexed with AFM13, suggesting that they can effectively eliminate lymphoma cells expressing CD30 and warrant further clinical testing.”
AFM13, a proprietary bispecific antibody, is designed to bind to CD16a on NK cells and activate them, while also targeting CD30 on lymphoma cells.
Initial studies on NK cells, which were isolated from the blood of patients with Hodgkin’s lymphoma, found that AFM13 formed a stable complex with NK cells and could induce NK cell-mediated killing of CD30+ cells. However, the activity of these cells was modest, so the researchers evaluated alternative NK cell sources.
Further studies suggested that NK cells derived from cord blood (cbNK cells) displayed consistent and improved activity against lymphoma with AFM13. The team further stimulated the anti-tumour immune activity of cbNK cells by pre-activation with a combination of the cytokines IL-12, IL-15, and IL-18.
Minimal side effects were observed in animal experiments using the pre-activated and expanded cbNK cells complexed with AFM13.
The treatment is currently being investigated in a phase 1 clinical study in patients with recurrent or refractory CD30-positive lymphoma.
Prof Rezvani said: “These findings suggest that, in animal models, ex vivo pre-activated and expanded cord blood-derived NK cells complexed with AFM13 were able to safely eliminate CD30+ lymphoma cells.
“We look forward to learning if this investigational therapy may provide benefits to patients with advanced lymphoma in the ongoing clinical trial.”
Kerbauy LN, Marin ND, Kaplan M, Banerjee PP, Berrien-Elliott MM, Becker-Hapak MK, 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. (2021) “Combining AFM13, a bispecific CD30/CD16 antibody, with cytokine-activated cord blood-derived NK cells facilitates CAR-like responses against CD30+ malignancies.” Clinical Cancer Research, doi: 10.1158/1078-0432.CCR-21-0164
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