Antibody Development against Antigens in Tumor Microenvironment

Creative Biolabs employs comprehensive technical platform, such as Hybridoma Platform, B-Cell Sorting Platform, Phage Display Platform, Membrane Protein Platform to provide our clients with antibody customization services. With Ph.D. level scientists and over a decade of experience in recombinant antibody production, antibody engineering, synthetic chemistry, and bio-conjugation, we are dedicated to helping our clients design and prepare antibodies with high affinity and good specificity against antigens in tumor microenvironment.

CAST Therapy

Antibody drug conjugates (ADCs) therapeutic effect was obtained after binding to cancer cells, normally followed by internalization. However, targeting the surface of tumor cells could be extremely challenging in stroma-rich solid tumors, where abundant intercellular stroma prevent cancer cell-specific monoclonal antibody (mAb) diffusion and become a barrier to ADCs reaching targeted cancer cells. Correspondingly, a new strategy is emerging which questions this. Stroma-targeting immunconjugates bound to the stroma to create a scaffold, from which sustained release of cytotoxic agent occurred and subsequently diffused throughout the tumor tissue to damage both tumor cells and tumor vessels. Cancer-stroma targeting (CAST) therapy was thus validated as a new modality of oncological therapy, especially for refractory, stromal-rich cancers. As shown in figure 1, the principle of CAST strategy is that immunoconjugates selectively extravasated from leaky tumor vessels, bound to the extracellular molecules in the stroma and created a scaffold from which effective sustained release of the low molecular weight (LMW) anticancer agents (ACA). This free LMW ACA can easily reach the cancer cells by diffusion through the stroma barrier.

Fig.1 New strategy of drug delivery using cytotoxic immunoconjugate directing tumor stroma. (Matsumura, 2012)

Antibody Strategy

At present, studies have reported monoclonal antibodies (mAbs) development against different components in tumor microenvironment. The tumor endothelial cells (ECs) components are readily accessible to drugs systemically delivered through the bloodstream, which could yield on-target exposure levels close to 100%. ECs are genetically stable, untransformed, and less likely to develop drug resistance, generally sensitive to the current payloads used in current ADC programs. Attentionally, the specific targeting of ECs may be restricted to cell surface antigens that internalize in order to prevent free drug release into the bloodstream. In contrast, targeting non-internalizing antigens present within the subendothelial modified extracellular matrix (ECM) and tumor stroma such as collagen IV and tenascin C may be both safe and efficacious. Tumor vascular-specific mAbs could be conjugated with drugs, which was proved to be applicable across a broad range of indications given the ubiquity of vessels within all solid tumor.

Fig.2 A schematic representation of the immunosuppressive tumor microenvironment. (Mirzaei, 2017)

With novel technology platform and professional experiment services, Creative Biolabs is committed to providing high-quality antibody products against antigens in cancer microenvironment to promote the progress of clients’ projects. Please feel free to contact us for more information and a detailed quote.

Reference

1. Matsumura, Y. Cancer stromal targeting (CAST) therapy. Advanced drug delivery reviews. 2012, 64(8), 710-719.
2. Mirzaei, H. R.; et al. Chimeric antigen receptors T cell therapy in solid tumor: Challenges and clinical applications. Frontiers in immunology. 2017, 8, 1850.