Hands Making a Heart Shape

Pipeline

Our goal is to develop, validate, and optimize therapeutically functional, anti-tumor monoclonal human recombinant antibodies and use these validated human antibodies to make antibody drug conjugates (ADCs) for cancer treatment.

The  Selection of Phage Accessible Recombinant Targeted Antibodies (SPARTA) approach is based on in vitro target receptor identification followed by in vivo antibody selection, using phage/yeast display, deep sequencing, and bioinformatics analyses. This approach will accelerate the development of antibody-based drugs for personalized medicine. The panels of monoclonal human antibodies identified in our studies represent therapeutic leads that will be optimized for delivery of therapeutic payloads (e.g. toxins, drugs, nanoparticles, etc.). We applied a hierarchical selection strategy to two tumor targets  with the objective to select human antibodies that localize to the tumor, bind specifically to the target receptor, and internalize into tumor cells and exhibit therapeutic properties for subsequent in vivo validation.

Our pipeline is applicable for any target and will address all core aspects of antibody generation including: 1) selection, sequencing, and expression, 2) characterization and 3) in vivo testing.

 


Schematic representation of recombinant antibody selection and validation in vitro and in vivo

Schematic

SELECTION OF PHAGE-DISPLAYED ACCESSIBLE RECOMBINANT TARGETED ANTIBODIES

Illustration
Staquicini & D’Angelo et al. JCI Insight 2018

SPARTA is a robust antibody discovery methodology. It combines an in vitro screening step of a naïve human antibody library against tumor targets, with in vivo selections based on tumor-homing capabilities of a pre-enriched antibody pool. This unique approach overcomes several rate-limiting challenges to generate human antibodies amenable to rapid translation into clinical applications.

ANTIBODY DRUG CONJUGATES (ADCS)

ADCs are drugs designed to target specific cancer cells and release a toxic drug into the cancer cell. ADCs work like a guided missile that seek out the targets on the cancer cell surface and deliver the payload (drug) into the cell. Since ADCs are design to target specific cancer cells and spare normal tissue, their use in cancer treatment is expected to result in less toxicity than a traditional chemotherapy.

ADCs are composed of 3 parts: An antibody that is specific for the type of cancer being, a cytotoxic chemotherapy drug, and a linker protein to hold the 2 parts together.

ADCS
JAMA Oncology September 26, 2019

MBRACE Therapeutics is developing ADCs against two novel cancer targets using human antibodies selected from SPARTA methodology. We will demonstrate that these ADCs are well tolerated and have robust anti-tumor activity against mouse xenograft/PDX models and are capable of inducing dose dependent tumor regression in cancer cell lines that express these targets on their cell surface. Our clinical development plan includes a personalized approach with a diagnostic test to select patients with tumors that have high expression of these targets.