- The poster presentation highlights the relevance of CD16A shedding for serial killing by AFM13-engaged natural killer (NK) cells
- It demonstrates the potential of AFM13 to induce serial killing, even in tumor cells with low target expression
HEIDELBERG, Germany, April 17, 2023 (GLOBE NEWSWIRE) -- Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, today presented a poster developed in collaboration with Prof. Björn Önfelt from the KTH Royal Institute of Technology and Karolinska Institute in Stockholm. The preclinical data demonstrate the ability of AFM13, Affimed’s CD16A/CD30-targeting innate cell engager (ICE®), to induce serial killing of tumor cells, while preserving CD16A shedding.
The poster, shown at the Annual Meeting of the American Association for Cancer Research (AACR) in Orlando, Florida, shared results from a live-cell microchip screening with single cell resolution. AFM13 increased NK killing efficiency of CD30-positive tumor cells via antibody-dependent cellular cytotoxicity (ADCC). For CD30 high-expressing targets, AFM13 and an anti-CD30 Fc-enhanced antibody triggered higher NK cell-mediated ADCC and serial killing than a monoclonal anti-CD30 antibody. However, for CD30 low-expressing tumor cells, AFM13 induced significantly stronger serial killing compared to both the monoclonal anti-CD30 antibody and the Fc-enhanced anti-CD30 antibody, which led to significantly higher cytotoxicity against the target cells.
In addition, the simultaneous administration of the CD16A shedding inhibitor Batimastat and AFM13 did not reduce the fraction of tumor-cell killing NK cells, but did reduce their ability to kill in series. With Batimastat, the fraction of NK cells performing at least one kill did not change, but significantly more NK cells died after their first killing. It was shown that more NK cells were stuck to target cells, when CD16A shedding was inhibited, and that they spent more time in conjugation. This leads to the hypothesis that CD16A shedding allows the NK cells to migrate to distantly located target cells after their first killing to proceed with additional AFM13-induced ADCC. However, after CD16A shedding inhibition, NK cells could still move around, dragging their target cells with them.
“AFM13 increased NK cell-mediated serial killing of tumor cells, even when they express low levels of CD30,” said Prof. Björn Önfelt. “And CD16A shedding seems to facilitate the migration of AFM13-armed NK cells to distant target cells.”
“It is impressive to see AFM13-engaged NK cells migrating at single cell resolution,” said Arndt Schottelius, chief scientific officer of Affimed. “With Prof. Önfelt’s microchip technology we can follow AFM13-engaged NK cells to see how they kill several tumor cells in sequence. This opens up new opportunities to gain a deeper understanding of their mechanism of action.”
Pre-complexed with cord blood-derived NK cells, AFM13 has already yielded very compelling clinical data in a Phase 1/2a study. Affimed is now on track to submit the IND for a Phase 2 combination study of AFM13 co-administered with NK cells in the first half of 2023.
The presented poster can be found on Affimed’s website at https://www.affimed.com/affimed-science-and-technology/publications-and-posters/.
AFM13 is a first-in-class tetravalent bispecific innate cell engager (ICE®) that uniquely activates the innate immune system to destroy CD30-positive hematologic tumors. AFM13 induces specific and selective killing of CD30-positive tumor cells, leveraging the power of the innate immune system by engaging and activating natural killer (NK) cells and macrophages. AFM13 is Affimed’s most advanced ICE® clinical program and was evaluated as monotherapy in a phase 2 trial in patients with relapsed/refractory peripheral T-cell lymphoma (REDIRECT, NCT04101331). Additional details can be found https://www.affimed.com/affimed-presents-final-data-demonstrating-safety-and-efficacy-of-afm13-phase-2-redirect-study-in-patients-with-heavily-pretreated-relapsed-or-refractory-peripheral-t-cell-lymphoma-at-the-american-asso/. In addition, The University of Texas MD Anderson Cancer Center is studying AFM13 in an investigator-sponsored Phase 1 trial in combination with cord blood-derived allogeneic NK cells in patients with recurrent or refractory CD30-positive lymphomas (NCT04074746).
About Affimed N.V.
Affimed (Nasdaq: AFMD) is a clinical-stage immuno-oncology company committed to give patients back their innate ability to fight cancer by actualizing the untapped potential of the innate immune system. The company’s proprietary ROCK® platform enables a tumor-targeted approach to recognize and kill a range of hematologic and solid tumors, enabling a broad pipeline of wholly-owned and partnered single agent and combination therapy programs. The ROCK® platform predictably generates customized innate cell engager (ICE®) molecules, which use patients’ immune cells to destroy tumor cells. This innovative approach enabled Affimed to become the first company with a clinical-stage ICE®. Headquartered in Heidelberg, Germany, with offices in New York, NY, Affimed is led by an experienced team of biotechnology and pharmaceutical leaders united by a bold vision to stop cancer from ever derailing patients’ lives. For more about the company’s people, pipeline and partners, please visit: www.affimed.com.
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