New antibody-based molecules for prostate cancer therapy

INTRODUCTION:

Prostate carcinoma is by far the most common non-cutaneous malignancy in men and the leading cause of cancer-related deaths. Current development of new diagnostic and therapeutic reagents is mainly focused on prostate-specific membrane antigen (PSMA) due to tight correlation between cancer development/progression and PSMA expression.

TECHNOLOGY (INVENTION) DESCRIPTION:

We have recently isolated and characterized in detail two new PSMA-specific antibodies. High specificity of these molecules for native PSMA is demonstrated by specific recognition of conformational epitopes on its surface combined with the lack of cross-reactivity to unrelated human proteins. Antibodies thus can be used in applications targeting PSMA in its native state. Using cancer cell lines and mouse xenograft model of prostate cancer we have shown that both molecules are suitable for in vitro and vivo applications.

ADVANTAGES OVER EXISTING SOLUTIONS:

Novelty of the molecules, in brief, is represented by superior affinities of described antibodies that are in subnanomolar range, moreover, described antibodies have approximately 10-times higher affinity for PSMA compared to leading second-generation antibody J591. In comparison to small molecules targeting PSMA, antibodies reveal significantly lower toxicity in non-target tissues such as salivary glands. Presented antibodies are therefore prime candidates for the development of the next-generation agents targeting PSMA.

DEVELOPMENT STATUS (STAGE):

Laboratory scale, data: in vitro - cell lines, in vivo pharmacodynamics and pharmacokinetics (mouse), crystal structure

PUBLICATIONS:

Nováková Z, Foss CA, Copeland BT, Morath V, Baranová P, Havlínová B, Skerra A, Pomper MG, Barinka C.Novel Monoclonal Antibodies Recognizing Human Prostate-Specific Membrane Antigen (PSMA) as Research and Theranostic Tools. Prostate. 2017 May;77(7):749-764. Ray Banerejee S, Kumar V, Lisok A, Plyku D, Nováková Z, Wharram B, Brummet M, Barinka C, Hobbs RF, Pomper MG. Evaluation of 111In-DOTA-5D3, a Surrogate SPECT Imaging Agent for Radioimmunotherapy of Prostate-Specific Membrane Antigen. J Nucl Med. 2018 Sep 20. pii: jnumed.118.214403.

IP PROTECTION STATUS:

patent application filed 2018

TECHNOLOGY / IP OWNERS :

Institute of Biotechnology CAS, v.v.i.