Affimed's lead program for Non-Hodgkins Lymphoma (NHL) has two product candidates: AFM11 and AFM12. These antibodies are bispecific TandAbs and work by binding to both malignant lymphocytes and the specific effector cells of the immune system: cytotoxic T-cells [AFM11] or Natural Killer (NK)-cells [AFM12]. In this way, the antibodies effect selective destruction of the malignant cells through antibody dependent cell mediated cytotoxicity (ADCC).
Non-Hodgkins Lymphoma
NHL is the collective term for the various types of tumors of the lymphatic system. It is a cancer of lymphocytes (a type of white blood cell) and is histologically distinct from Hodgkin's Disease, another subtype of lymphoma. Over 80% of all malignant lymphomas are NHL, over 90% of which are due to malignant B-lymphocytes, and only 10% are due to malignant T-lymphocytes. Current therapeutic approaches like chemotherapy or radiation are able to achieve complete remission in more than 50% of the patients, although through this treatment patients can be afflicted with serious side effects. Rituximab (IDEC), a monoclonal antibody targeting CD20, is the only current antibody therapeutic indicated for NHL.
AFM11
AFM11 is a bispecific TandAb targeting CD19, one of the most frequently expressed surface markers on Non-Hodgkin B-lymphocytes, and CD3, a surface receptor on cytotoxic T-cells. CD3 is an especially well characterized receptor for the binding and activation of T-cells. The principle of action of AFM11 is unique. On the one hand, the bispecificity of this TandAb specifically enables an activation of T-lymphocytes. On the other hand, the unique antibody format achieves a higher therapeutic efficacy (by improving affinity, pharmacokinetics and stability) and due to the absence of the constant domain, less side effects can be expected. Of particular interest is that T-cell activation is dependant on the binding of the antibody to the target.
AFM11 has completed preclinical studies establishing proof of concept in vitro as well as in vivo.
AFM12
AFM12 is similarly a bispecific TandAb targeting the malignant B-lymphocyte marker, CD19, and CD16, a surface receptor on NK cells. The principle is the same as for AFM11, uniting the malignant lymphocytes with the effector (NK) cell that will destroy it.
In vitro tests have shown that AFM12 is more effective at lysing malignant B cells than either Rituximab or an anti CD19 IgG.
Clinical trials
Affimed's intends is to compare AFM11 and AFM12 in relevant in vitro and in vivo models and to select the most promising NHL candidate for clinical development.