Peptide-Based Immunogen Design

Immunogen design: Therapeutic vaccines derived from synthetic conformational peptide antigens that mimic target proteins

Immunotherapy is a rapidly emerging field of new therapies for cancer and other currently incurable diseases. A major benefit of this approach is the prospect of precisely targeted therapies with a considerably lower risk of side effects and minimal discomfort for 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 next step is to have the body produce the antibodies itself via active immunization. Combining active and passive immunization has many advantages, including opening up new opportunities for the development of additional treatment options, as well as creating more advanced and effective treatment regimens.

Unique technology platform

Pepscan has extensive experience in discovery, development and design of peptide immunogens derived from synthetic peptide antigens. Over the years, we have developed a unique technology platform for the generation of these antigens based on the mimicry of target proteins with conformational peptides.

With our drug discovery services, Pepscan has assisted in the discovery and development of several peptide immunogens. Our most advanced peptide immunogen to date is currently in clinical development by a partner.

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.

passive-immunisation-2 passive-immunisation

Treatment with pooled anti‐hVEGF26‐104 serum as well as bevacizumab inhibited the growth of LS174T human colon carcinoma compared to PBS treated tumors, as quantified by tumor volume (A) and tumor weight (B)
Reference: Wentink et al.: Targetted vaccination against teh bevacuzimab binding site on VEGF using 3D-structured peptides elicitsefficient antitumor activity. Published on-line before print, October 17, 2016, doi: 10.1073/pnas.1610258113
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