NSFTA · New Strategies For Therapeutic Antibodies – Synthetic bispecific antibodies & Antibody-Drug Conjugates with controlled drug loading. General methods for unexplored ADCs and personalised therapies.

New Strategies For Therapeutic Antibodies – Synthetic bispecific antibodies & Antibody-Drug Conjugates with controlled drug loading. General methods for unexplored ADCs and personalised therapies.

Antibodies can recognize invaders and call immune cells in order to destroy them. They notably recognize cancer cells. It is possible to attach toxic drugs to an antibody so they are driven directly to the cancer cells to destroy them, sparing the healthy cells and avoiding secondary effects. An antibody is a chemical structure possessing “chemical hooks” on its surface. Chemical reactions allow attaching interesting payloads (e.g. drug) to these antibody's hooks. However, antibodies possess on their surface a multitude of identical hooks. As a consequence, it is hard to have perfect control over the number and location of the payloads being attached. For instance, if the aim is to attach only two payloads per antibody, it will rather end up with a "mixture", a statistical distribution of antibodies having 0 or 1 or 2 or 3 or 4 elements attached. The lack of control over the number of payloads per antibody is problematic regarding multiple aspects: 1. It is hard to generate and identify the optimal ratio payload/antibody for the best therapeutic result. 2. Regarding validation of the production process, homogeneity is preferred. Ideally, only one type of ratio should be obtained. 3. New developments consist in attaching different types of payloads to the antibody, in order to get a synergistic effect. The challenge is improved when attaching two different drugs to the antibody. Besides, “bispecific antibodies” are a new sort of antibody, able to recognize two different targets. They are kind of a “mix” between two antibodies. Their capacity to act simultaneously on two different targets is very useful for cancer treatment, but they are made through bioengineering: an expensive and time-consuming process, especially when various bispecific antibodies are meant to be evaluated (“screening” process). Thus, a faster method to create bispecific antibodies would be helpful to speed up screening processes. Developing chemical methods that allow attaching active compounds to the antibody with perfect control is of huge importance. In the long-term view, this should allow to develop optimized treatments and thus benefit patients. Regarding the easier and faster generation of bispecific antibodies, this could highly improve the number of bispecific antibodies evaluated and thus speed up the finding of new treatments. Overall objectives: 1. To develop a method that allows attachment of one type of payload to an antibody in a controlled manner. Notably, having access to various and rare drug/antibody ratios with the same generic method is a pursued goal. 2. To develop a method that allows attachment of different payloads to an antibody in a controlled manner. 3. To develop a fast and generic method to generate bispecific antibodies without requiring bioengineering, but rather using chemical reactions.

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