Antibody Development against Antigens in Tumor Stroma and Vasculature

As a well-recognized leader with decades of experience in monoclonal antibodies (mAbs) preparation, Creative Biolabs is dedicated to the development of new therapeutic agents. Now, we offer global clients with comprehensive antibody development services for antigens in tumor stroma and vasculature.

Tumor Stroma and Vasculature

There is sufficient evidence in the preclinical and clinical setting that components of the tumor stroma and of the vasculature subendothelial extracellular matrix could be valuable target antigens. The tumor stroma is an active player in cancer. All tissues require an extracellular network to provide structural support and facilitate the continuous communication between cells maintaining tissue homeostasis. An important regulator of normal tissue behavior is the extracellular matrix (ECM), which surrounds cells and is composed of collagen, laminin, fibronectin, and heparan sulfate proteoglycans (HSPGs) and so forth. As shown in figure 1, the basement membrane (BM), one specialized ECM, separates the epithelium from the stroma and underlies endothelial cells, pericytes, and other cell types. Endothelial cells are untransformed, genetically stable, and less likely to develop drug resistance, and generally sensitive to the current payloads used in current antibody-drug conjugates (ADCs) programs.

Fig.1 Overview of tumor microenvironment and therapeutic strategies. (Joyce, 2005)

It is now universally acknowledged that in order for a tumor to grow beyond a certain size, it needs to recruit its own blood supply to deliver oxygen and nutrients. The tumor vasculature is derived by angiogenesis, new blood vessel growth from pre-existing vessels. Considering the ubiquity of vessels within all solid tumors, tumor vascular-specific antibodies could be applicable across a broad range of indications in therapeutic agents development.

Antibody Strategy

Stroma-targeting immunoconjugates 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 vessels and tumor cells. To date, it has been discovered that extracellular drug release in the tumor microenvironment is possible with non-internalizing ADCs bearing classical linkers. Monoclonal antibodies (mAbs) against antigens like collagen IV, fibrin and tenascin C which is abundantly found in the stroma of solid tumors, especially invasive tumors, have been developed and subsequently conjugated with payload thus forming non-internalizing ADCs. Non-internalizing ADCs have the ability to induce a potent anticancer activity in vivo when used with a suitable payload and may target a broad variety of different malignancies, including lymphomas and, potentially, certain leukemias. The ADCs is stable in plasma, and diffused throughout the stromal barrier, resulting in potent anti-tumor activity by damaging both tumor-associated vessels and tissues.

Fig.2 Target antigens for ADCs in solid tumors. (Diamantis, 2016)

Creative Biolabs has gained significant knowledge of antibody development. We are glad to share our experience and help our customers with this tragically important step in therapeutic agents development. For more information about antibody development services for antigens in tumor vasculature and stroma or a detailed quote, please feel free to contact us .

References

Joyce, J. A. Therapeutic targeting of the tumor microenvironment. Cancer cell. 2005, 7(6), 513-520.
Diamantis, N.; Banerji, U. Antibody-drug conjugates-an emerging class of cancer treatment. British journal of cancer. 2016, 114(4), 362.

For Research Use Only. NOT FOR CLINICAL USE.