ICE® (innate cell engager) molecules bring together the innate immune cell (NK cell or macrophage) and tumor cell by binding to the CD16A receptor on innate immune cells and a specific receptor on the tumor cells. Once this bridge is established, the immune cell is activated to release factors that directly kill the tumor cell.

In contrast with other antibody-based therapeutics, ICE® (innate cell engager) molecules generated from the ROCK® (Redirected Optimized Cell Killing) platform avoid competition with the body’s own circulating serum IgG by binding efficiently and stably to a unique epitope on the CD16A receptor on NK cells and macrophages with high affinity and avidity.1,2


Our ICE® (innate cell engager) molecules restore dysregulated NK cells, and increase cytotoxic activity
of healthy donor–derived NK cells

ICE® (innate cell engager) molecules bridge innate immune and tumor cells and restore the innate cells’ ability to kill tumor cells

Innate immune cell reactivation through ICE® (innate cell engager) molecules enables tumor recognition and initiates an immune response. When the NK cell and tumor cell are brought together, the innate immune cell releases perforins to create pores in the tumor cell membrane through which granzymes enter the tumor cell, triggering apoptosis and resulting in tumor cell death.


Lighting the way with clinical results: we are creating success with monotherapies and combination therapies

AFM13, a first-in-class ICE® (innate cell engager) molecule targeting patients with CD30-positive lymphomas,4 showed antitumor responses in a Phase 1/2 trial as a monotherapy in 15 patients with T-cell lymphomas and cutaneous involvement (44% ORR).5 When used in combination with allogeneic NK cells (pre-complexing of AFM13 + cbNK), early clinical data in heavily pre-treated patients with Hodgkin lymphoma show a reduction in tumor burden as well as favorable safety.6 When used in combination with an anti–PD-1 antibody in Hodgkin lymphoma, AFM13 demonstrated promising signs of efficacy, including an ORR of 88% at the highest treatment dose, as well as a CR of 46% (per independent assessment).7 Both ORR and CR rates were higher in combination with AFM13 than with the anti–PD-1 antibody alone.7


Potential to treat various solid tumor types with a more acceptable safety profile while remaining immune to the challenge of resistance8

AFM24, an EGFR-directed ICE® (innate cell engager) molecule, represents a distinctive mechanism that engages innate immune cells by recruiting NK cells and macrophages to the site of the tumor for effective and efficient tumor-cell killing.8 The differentiated MOA does not rely on the EGFR signaling pathway for tumor killing but instead uses EGFR as a docking site only.8 Unlike existing therapies, AFM24 can be used in all EGFR-expressing tumors, including tumors that have become resistant to signaling inhibition.8

AFM24 induces ADCC in KRAS/BRAF-mutated cell lines to a comparable extent as in nonmutated cell lines, which indicatively proves the hypothesis that the novel mechanism does not rely on EGFR signaling.8 The strong binding affinity and ability to target with low antigenic expression differentiates AFM24 from other treatments.8

Broad applicability expands horizons for those we can help

Preclinical data of AFM24 indicate promising efficacy across a wide variety of solid tumor types, including, but not limited to lung, colon, renal, and gastric cancers.8 Clinical data are currently being generated, and if successful, AFM24 could address a significant patient population underserved by current therapies. Emerging clinical data of AFM13 demonstrate impressive efficacy across a number of lymphoma types, including T-cell lymphoma and Hodgkin lymphoma.5,7

We are awaiting highly anticipated results in several EGFR-expressing tumors (eg, lung, RCC, CRC), T-cell lymphoma, Hodgkin lymphoma, and additional CD30-positive lymphomas.

Creating ICE® (innate cell engager) molecules using our proprietary
ROCK® platform

Affimed’s ICE® (innate cell engager) molecules are built on the ROCK® platform—the most clinically advanced technology for designing innate immunity therapies that can be tailored to specific patient populations, allowing for the creation of powerful monotherapies and I-O combination treatments.

Learn more about the ROCK® platform

ADCC=antibody-dependent cellular cytotoxicity; cbNK=cord blood–derived natural killer cell; CD=cluster of differentiation; CR=complete response; CRC=colorectal cancer; EGFR=epidermal growth factor receptor; I-O=immuno-oncology; IgG=immunoglobulin G; MOA=mechanism of action; NK=natural killer; ORR=objective response rate; PD-1=programmed cell death protein 1; RCC=renal cell carcinoma.

References: 1. Ellwanger K, Reusch U, Fucek I, et al. Redirected optimized cell killing (ROCK®): A highly versatile multispecific fit-for-purpose antibody platform for engaging innate immunity. MAbs. 2019;11(5):899-918. 2. Wingert S, Reusch U, Baez A, et al. CD16A-specific tetravalent bispecific immuno-engagers potently induce antibody-dependent cellular phagocytosis (ADCP) by macrophages. Poster presented at: American Society of Hematology (ASH) Annual Meeting; December 1-4, 2018; San Diego, CA. 3. Zhao X, Rajasekaran N, Reusch U, et al. In vitro and in vivo characterization of CD19/CD3 Tandab AFM11 and CD19/CD16A Tandab AFM12 targeting NHL. Poster presented at: American Society of Hematology (ASH) Annual Meeting; December 5-8, 2015; Orlando, FL. 4. Rothe A, Sasse S, Topp MS, et al. A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2015;125(26):4024-4031. 5. Sawas A, Chen P, Vlad G, et al. Clinical and biological evaluation of the novel CD30/CD16A tetravalent bispecific antibody (AFM13) in relapsed or refractory CD30-positive lymphoma with cutaneous presentation: a biomarker Phase Ib/IIa study (NCT03192202). Poster presented at: American Society of Hematology (ASH) Annual Meeting; December 1-4, 2018; San Diego, CA. 6. Rezvani K. CAR NK cells: a drive to the future of cell therapy. Presented at: American Association for Cancer Research (AACR) Annual Meeting; April 10-15, 2021; Virtual. 7. Bartlett NL, Herrera AF, Domingo-Domenech E, et al. A phase 1b study of AFM13 in combination with pembrolizumab in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2020;136(21):2401-2409. 8. Reusch U, Damrat M, Wingert S, et al. AFM24, a bispecific EGFR/CD16A innate cell engager with the potential to overcome resistance to current targeted treatments for EGFR-positive malignancies. Poster presented at: American Association for Cancer Research (AACR) Annual Meeting; June 22-24, 2020; Virtual. Poster 5659.