Retrogenix® Cell Microarray Technology Oncology Applications

The Retrogenix^® Cell Microarray can be leveraged to screen both whole CAR cells and scFvs for specificity, against a comprehensive human cell surface protein library. The critical nature of identifying the off-targets of CAR cells before the therapeutic is deployed to clinical trials or patients makes the Retrogenix^® Cell Microarray an invaluable tool in the development of safe oncology therapies, screening candidate molecules against over 6,300 human cell surface proteins. This technology was used to support the licensing application for Novartis’ Kymriah therapy, the first CAR-T immunotherapy ever to receive FDA approval.

A Recent Scripps Study Shows That ROR2 Is a Promising Candidate Antigen for Cancer Therapy

Antibodies are widely used as cancer therapeutics, but their current use is limited by the low number of antigens that are solely present on cancer cells which can serve as useful targets. One such antigen – receptor tyrosine kinase-like orphan receptor 2 (ROR2) – is normally expressed only during embryogenesis and then is tightly down-regulated, however, it is up-regulated in a diverse set of cancers. This includes solid malignancies such as renal cell adenocarcinoma and subsets of breast cancer, as well as hematologic malignancies, such as multiple myeloma. As such, ROR2 represents a promising candidate antigen for antibody-based cancer therapy.

Previous research by the Scripps Research Institute had identified several potential ROR2 antibody candidates by mining a large library of novel rabbit antibodies (>10 billion) that had been generated through phage display. A new paper by the same team, describes the process and results of affinity maturation and humanization of one of these rabbit mAbs. The candidate antibody was selected as it binds both human and mouse ROR2 but not to other human cell-surface antigens including human ROR1 (which has 58% amino acid sequence identity with ROR2).

The affinity matured and humanized mAb maintained strong affinity to ROR2. It was also shown to retain its specificity to ROR2 when screened against 5,500+ plasma membrane and secreted protein targets using the Retrogenix^® Cell Microarray Technology. Following conversion to a T-cell engaging bispecific antibody, the ROR2 candidate displayed potent cytotoxicity toward ROR2-expressing cells.

The authors anticipate that this humanized affinity matured mAb will find application for antibody-based therapy of ROR2-expressing cancers. The paper, co-authored by Scripps researchers and scientists from Retrogenix^®, has been published in the Journal of Biological Chemistry. Please click here to read more about assessing mAb specificity

Strategic Alliance with Resonant Therapeutics to Identify Targets of Anti-tumor Antibodies

High Peak UK, Cambridge, MA and Houston, TX USA - Retrogenix^® and US-based Resonant Therapeutics, Inc. announced today that they have entered into a non-exclusive strategic partnership to identify the targets of Resonant antibodies directed against the tumor microenvironment.

Resonant exploits its proprietary IMPaCT tumor microenvironment models and data platform to discover novel, unappreciated targets and functionally active anti-tumor antibodies for difficult to treat tumors. By recapitulating the tumor microenvironment and using a live-cell, function-first approach, Resonant’s platform generates therapeutic candidates that would not be discovered by other methods with unprecedented speed. The target screening performed by Retrogenix^® will focus on hundreds of novel, prioritized antibodies in Resonant’s collection.

Targets within the tumor microenvironment may include both plasma membrane proteins as well as proteins typically secreted into the extracellular space. Retrogenix’s^® extensive library of human proteins make it uniquely placed for assessing candidate antibodies for target binding.