Antibody Development for Antigens on Tumor-associated Stromal Cells

Creative Biolabs provides customized antibody development services against antigens on tumor-associated stromal cells by advanced technical platform to help your projects. With years of experience in antibody production and bio-conjugation, our professional scientists are committed to providing high-quality services to promote your project.

Carcinoma-associated fibroblasts (CAFs)

Cellular and molecular crosstalks between cancer and non-cancer tumor-associated cells result in tumor growth and metastatic spreading. During carcinoma development, tumor cells secrete signaling molecules that influence the surrounding non-cancer cells, which, in return, favor tumor cell growth, survival, migration, and metastasis. Therefore, besides targeting antigens in tumor stroma and vasculature, targeting tumor-associated cells is another interesting approach. For instance, cancer-associated fibroblasts (CAFs), endothelium cells and pericytes are emerging fields in cancer therapeutics as these cells play a crucial role in promoting angiogenesis and tumor growth via paracrine signals.

CAFs are the most abundant population of non-cancer cells found in various human cancers, including breast, lung, prostate, colon, and pancreas and thought to promote tumor growth through immune suppression and secretion of factors that stimulate cancer cell proliferation, invasion, and angiogenesis. CAFs create a suitable "soil" for tumor origination, secrete a large number of growth factors promoting tumor growth and angiogenic factors promoting tumor angiogenesis. In addition, CAFs attract a large number of inflammatory cytokines and secrete a great number of soluble products promoting tumor cell invasion and metastasis. Therefore, CAFs may become new targets for targeted cancer therapy, and provide new ideas for the clinical cancer comprehensive treatment.

Therapeutic targeting of the key signalling pathways associated with CAFs. Fig.1 Therapeutic targeting of the key signalling pathways associated with CAFs. (Togo, 2013)

Tumor Endothelium

Tumor endothelium also plays a critical role in promoting tumor growth and metastasis, and agents that block angiogenesis through VEGF (vascular endothelial growth factor) pathway inhibition is an important component of cancer therapies. The endothelium is a target for therapeutic and diagnostic interventions in a plethora of human disease conditions including ischemia, inflammation, edema, oxidative stress, thrombosis and hemorrhage, and metabolic and oncological diseases. The specific targeting of endothelial cells may be restricted to cell surface antigens that internalize in order to prevent free drug release into the bloodstream. VEGFR2, in particular, is a promising candidate.

A schematic representation of SLIT/ROBO signalling during angiogenesis. Fig.2 A schematic representation of SLIT/ROBO signalling during angiogenesis. (Yadav, 2014)

Antibody Strategy

While tumor cell-directed antibody-drug conjugates (ADCs) frequently target only a limited number of tumor types or a subset of patients with defined alterations, ADCs that react with tumor-associated stroma can potentially target many different tumor types. Advances in genomics and proteomics have revealed antigens highly expressed on tumor-associated stroma, which may have the specificity needed to develop a stromal cell-directed ADC, such as tumor endothelial markers, receptors. Tumor-associated stromal cells represent a reservoir of potential ADCs target. Approaches that target these alterations may provide pan-tumor treatment options, making CAFs and other stromal cells potentially more amenable to therapeutic intervention.

With expertise and dedication, advanced antibody design platform and services from Creative Biolabs will be your best companion in generating customized antibodies. Please contact us for more information and a detailed quote.

References

  1. Togo, S.; et al. Carcinoma-associated fibroblasts are a promising therapeutic target. Cancers. 2013 5(1), 149-169.
  2. Yadav, S. S.; Narayan, G. Role of ROBO4 signalling in developmental and pathological angiogenesis. BioMed research international. 2014.

For Research Use Only. NOT FOR CLINICAL USE.


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