Therapeutic vaccines based on synthetic conformational peptide antigens that mimic target proteins
Immunotherapy is a rapidly emerging field providing new therapies for cancer and other at present incurable diseases. A major attraction of this approach is that it offers the prospect of precisely targeted therapies with greatly reduced risk of side effects and minimal discomfort to the patient.
The mainstay of current immunotherapies is formed by antibody-based products. Therapeutic antibodies are produced outside the body and administered by intravenous infusion. The obvious next step is to have the body produce the antibodies itself via active immunization. This has many advantages including creating new opportunities for the development of additional treatment options and the creation of more advanced and effective regimens by combining active and passive immunization.
Pepscan has thorough experience in the discovery and development of therapeutic vaccines based on synthetic peptide antigens. Pepscan has over the years developed a unique technology platform for the generation of these antigens, based on mimicry of target proteins with conformational peptides.
As part of our drug discovery services Pepscan has assisted in the discovery and development of several therapeutic vaccines, of which the most advanced is currently in clinical development by a partner. Contact us for more information.
Case example: a peptide-based therapeutic vaccine targeting hVEGF
Targeting VEGF is a well established way of inhibiting angiogenesis and is applied in the treatment of different types of tumors. Pepscan recently developed a peptide-based therapeutic vaccine targeting hVEGF. We designed and synthesized a truncated 79-mer hVEGF-derived peptide (VEGF26-104), which contains an intact cys-knot fold (i.e. 3 SS-bonds). Maintaining this three dimensional structure is crucial for the desired immunogenic activity.
Passive immunization with pooled antiserum containing of hVEGF26-104 antibodies in LS174T human colon cancer bearing nude mice inhibited tumor growth as well as tumor vascularity, with an effect comparable to bevacizumab (Avastin®). The ability of prophylactic immunization with adjuvanted mVEGF26-104 was demonstrated by the significantly inhibition of the growth of B16F10 melanoma in immunocompetent mice.
The preclinical study program demonstrated that hVEGF26-104, a structured peptide mimic of hVEGF165, is able to induce neutralizing polyclonal anti-VEGF antibodies with potent tumor inhibiting capacities.
This vaccine has been partnered with Immunovo and is currently studied in a combined Phase-I/IIa clinical trial.