PhD defence A.D.Q. Al-Qahtani

Production of novel protein therapeutics to improve targeted cancer therapy

Cancer is one of the leading cause of death worldwide and in Qatar. Conventional cancer therapies are the main stream for treatment but with severe side effects. Targeted cancer therapy, including cancer immunotherapy, is an emerging treatment with tolerable side effects. The work Alanod Al-Qahtani presented, deals with two different approaches for targeted cancer treatment; Antibody Directed Enzyme Pro-drug Therapy (ADEPT) and the Targeted tumor superantigens (TTS). ADEPT is a two steps therapy, the first include the injection of antibody-enzyme (glucarpidase) conjugate and the second, is the injection of the Prodrug. The enzyme will produce a powerful cytotoxic drug in the vicinity of the cancer site. ADEPT should be done in repeated cycles which lead to production of antibody against the enzyme and undermined the treatment. The work presented overcome many of the ADEPT pitfalls: 1. Isolation and molecular characterization of a novel glucarpidase to evade the immune system2. Production of two long acting “biobetter” glucarpidase variants which are proteases resistant. 3. Production of novel glucarpidase variants with enhanced enzyme activity, by DNA mutagenesis.

The second part of the work deals with Superantigens. They are a class of antigens that cause non-specific activation of T-cells and massive cytokine release which cause among other, sever hypotension. Part of the work successfully, identified the regions on superantigen, SPEA which involved in causing hypotension. This work will pave the way to produce novel variants of superantigens with less or no hypotension side effect and will be suitable for tolerable caner immunotherapy.

Promotores: Prof.dr. A.S.S. Dömling