HOUSTON – Natural killer cells activated by cytokines (NK) derived from umbilical cord blood, combined with a bispecific investigational antibody targeting CD16a and CD30 known as AFM13, showed potent antitumor activity against CD30 + lymphoma cells, according to a new study preclinical research from the University of Texas MD Anderson Cancer Center.
The findings were published today in Clinical Cancer Research, a journal of the American Association for Cancer Research. These results led to the launch of a Phase I clinical trial to evaluate the combination of cord-derived NK cells (cbNK cells) with AFM13 as an experimental cell-based immunotherapy in patients with CD30 + lymphoma.
“The development of new therapies with NK cells has been a priority for my team at MD Anderson to address unmet needs for the treatment of hematological cancers and solid tumors,” said senior author Katy Rezvani, MD, Ph.D., professor of Stem Cell Transplantation and cell therapy. “This preclinical work provided proof of principle for NK cells pre-complexed with AFM13, suggesting that they can effectively eliminate lymphoma cells that express CD30 and warrant further clinical testing.”
Natural killer cells are part of the innate immune system and act naturally to eliminate cancer cells from the body. However, they have limited persistence on their own, and tumors can develop mechanisms to escape NK cells, explained Rezvani. Therefore, his research team has been working to develop approaches to increase the antitumor effectiveness of NK cells.
AFM13 from Affimed is a proprietary bispecific antibody designed to bind to CD16a in NK and CD30 cells in lymphoma cells. Initial studies with NK cells 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 CD30 + cell death. However, the activity of these cells was modest, leading researchers to evaluate alternative sources of NK cells.
Other experiments suggested that cbNK cells, isolated from cord blood donations made to the MD Anderson Cord Blood Bank, exhibited consistent and improved activity against AFM13 lymphoma compared to other sources of NK cells. The researchers were able to further stimulate the anti-tumor immune activity of cbNK cells by pre-activation with a combination of cytokines IL-12/15/18.
In animal models, pre-activated and expanded cbNK cells complexed with AFM13 resulted in better tumor control and survival compared to controls, with minimal side effects observed.
“These findings suggest that, in animal models, pre-activated and expanded ex vivo umbilical cord-derived NK cells complexed with AFM13 were able to safely eliminate CD30 + lymphoma cells,” said Rezvani. “We are looking forward to whether this experimental therapy can provide benefits for patients with advanced lymphoma in the ongoing clinical trial.”
The provisional results in three patients from the Phase I clinical trial were presented by Rezvani at the 2021 Annual Meeting of the American Association for Cancer Research (AACR) online. The trial is in progress.
This research was supported in part by the National Institute of Health (NIH) (1 R01 CA211044-01, 5 P01CA148600-03, P50CA100632-16, CA016672, K12CA167540 and R01CA205239), the National Cancer Institute (NCI) (P30CA091842), the NIH / NCI SPORE in Leukemia (P50CA171963) and the like. A complete list of collaborating authors and their disclosures can be found here.
MD Anderson has an institutional financial conflict of interest with Affimed related to this research and, therefore, has implemented a Plan for the Management and Monitoring of Conflicts of Institutional Interests
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