Clinical Data Preclinical characterization of the ICE® AFM28
The novel ICE® AFM28 is designed to target CD16A on innate immune cells and CD123 on tumor cells in relapsed or refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). CD123 is almost universally expressed on leukemic blasts and leukemic stem cells (LSCs) and thereby represents a promising target in both indications.
The results revealed that target cell lysis via NK cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC), even at low CD123 expression, was more pronounced compared to conventional anti-CD123 antibodies. In addition, AFM28 showed a 100-fold more potent NK cell activation in an ex vivo analysis, compared to Fc-enhanced IgG1 antibodies. When compared with a CD123-targeting T cell-engaging bispecific antibody, AFM28 activity was associated with substantially lower levels of inflammatory cytokine release suggesting low risk of cytokine release syndrome. In support of these findings, administration of AFM28 to cynomolgus monkeys induced the effective depletion of CD123+ target cells and was well tolerated. AFM28 is currently being prepared for clinical evaluation. The properties of the preclinical characterization make it an interesting candidate for combination approaches with allogeneic NK cell products.
“There is an urgent need for relapsed or refractory AML and MDS patients and targeting the innate immune system – either alone or in combination with adoptive NK cells – holds promise for these patients,” said Dr. Arndt Schottelius, CSO of Affimed. “Our data suggests that AFM28 engages NK cells to lyse CD123-positive leukemic blasts and leukemic stem cells. This is a critical step in achieving long-lasting remissions.”
Cryopreservation of NK cells pre-complexed with innate cell engagers (CAR-like NK cells)
Pre-complexing NK cells with the ICE® AFM13 generates chimeric antigen receptor (CAR)-like NK cells. Our preclinical assays demonstrate that anti-tumor efficacy of AFM13 pre-complexed NK cells was comparable to NK cells that were combined, though not pre-complexed with AFM13. Furthermore, the data showed that tumor cell lysis was enhanced compared to a Fc-enhanced antibody approach.
Retaining biological activity and specificity after cryopreservation is a prerequisite to enable the development of pre-complexed off-the-shelf CAR-like NK cell products. Our results confirmed that the efficacy of tumor cell lysis by AFM13-pre-complexed NK cells, was virtually unaffected after one cycle of cryopreservation at -80°C.
“The data are the basis to develop an off-the-shelf precomplexed NK cell product of our ICE® molecules and mark an important milestone,” said Dr. Arndt Schottelius, CSO of Affimed. “This is especially encouraging as we recently announced very promising data of the Phase 1-2 study at The University of Texas MD Anderson Cancer Center that evaluates AFM13 pre-complexed with NK cells in patients with CD30-positive lymphomas revealing a 100% objective response rate in 13 patients who received the recommended phase 2 dose.”