New Nanobody vs CD38 outperforms FDA-approved Antibodies for treatment of multiple Myeoloma
A new single domain antibody (Nanobody NbC6) against CD38 shows superior properties over FDA-approved Antibodies like Isatuximab and Daratumumab. Its Higher Affinity, smaller size and improved killing efficiency makes it a superior candidate for treatment of Multiple Myeoloma. Additionally, a combination with at least one FDA-Approved Antibody is possible further increasing the efficiency.
Challenge
Nowadays the first choice for therapy of Cancer are antibody based drugs as they are precise, easy to administer and have comparably little side effects. Therapeutic antibodies can be used to activate the immune system, but binding also induces natural killing mechanisms like “Antibody Derived Cellular Cytotoxicity” (ADCC) or “Complement-Dependent Cytotoxicity” (CDC). Maybe the most prominent example for anti-cancer antibodies is the CD38 antibody based cancer treatment against multiple myeloma.
CD38 is a cell surface membrane protein expressed in many immune cell types, but is otherwise nearly not expressed at all on normal cells. In contrast it is highly overexpressed in some cancer types: e.g. Lymphoma, Myeloma and Leukemia. Two FDA approved drugs (Daratumumab and Isatuximab), which are based on CD38 antibodies are already on the market. In 2024 Daratumumab was the drug with the sixth highest sales worldwide. However the efficiency of these AB-based drugs varies and cannot completely cure cancer for many patients. Consequently, several clinical trials aiming to enhance efficiency of the therapy are running. A new CD38 antibody with increased efficiency is highly desirable, would create benefit for patients and has the potential to become a best seller.
Our Solution
A superior single domain antibody (the Nanobody NbC6) was developed at the University Medical center Göttingen. It shows a factor of 30-100 higher affinity to CD38 compared to Daratumumab and Isatuximab. This higher affinity is also reflected by a higher killing efficiency in CDC and ADCC assays (Figure 1). Especially a combined treatment of cells with NbC6 and Isatuximab shows highly improved efficacy.
Figure 1 - Killing Essays: Cell death measurement: fluorescent signal, data normalized to RAMOS + NK without antibody. NbC6hrlgG1=NbC6 Minibody.
Left: Complement-Dependent Cytotoxicity (CDC). Percentage of dead human B lymphoma cells (RAMOS) depending on the antibody concentration in the presence of human serum. Right: Antibody-Dependent Cellular Cytotoxicity (ADCC) Assay: RAMOS cells incubated with primary NK cells in the presence of different antibodies at 1pM concentration.
Beeing a Nanobody, NbC6 is nearly 10 times smaller in size and thermally more stable compared to FDA-approved Antibodies against Multiple Myeloma, An improved tissue penetration and cheaper production and storage can be anticipated.
Advantages
- A therapy with NbC6, especially in combination with Isatuximab will show a very high efficiency
- Less side effects can be anticipated, due to very high specificity for CD38
- Cost effective production and simple storage (advantage of Nanobodies over Antibodies)
- Superior binding affinity and killing efficiency already at low concentrations
- A combination with Isatuximab is possible, further increasing efficiency
- smaller size allows good tissue penetration
Applications
- Treatment of Multiple Myeloma, Leukemia or Lymphoma either standalone or in combination with Isatuximab
- Its high affinity, specificity and small size makes NbC6 an excellent Marker for CD38 in clinical and research applications
Development Status
Preclinical: Proof of affinity and killing efficiency in living cells
Patent Status
A Priority patent application has been filed in the name of the University Medical Center of Göttingen – Worldwide IP-Rights possible.
Contact
Dr.Martin Andresen
Patent Manager Life Sciences
E-Mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
Tel.: +49 551 30724 150
Reference: BioT-2612-UMG
Tags: Daratumumab, Isatuximab, tumor micro environment, TME, immune suppresion, Nanobody, CD38
