Metastatic colorectal cancer can now be treated with the help of monoclonal antibodies. Cetuximab and Panitumumab are examples of appropriate medicines. Point of application of drugs is always the epidermal growth factor receptor (EGFR). Clinical trials for monotherapy hereby show response rates of around 10%.
Unfortunately, the positive detection of EGFR expression by immuno-staining is not reliable. For the preservation of clinical results must therefore be an intensive search for alternative, more predictive biomarkers. The oncogenic activation of the EGFR signaling pathways, such as the mutation of the KRAS, BRAF or PIK3CA oncogenes, or the inactivation of the PTEN tumor suppressor gene is of paramount importance for the progression of colorectal carcinomas. KRAS mutations occur in 35-45% of patients with colorectal carcinoma and appears as an important predictive marker of resistance to panitumumab or cetuximab treatment. Wild-type KRAS-carrying colorectal tumors showing mutation of BRAF or PIK3CA or loss of PTEN expression may be associated with resistance to EGFR-targeted monoclonal antibody treatment. These additional biomarkers require further validation before including them into clinical practice. But the development of new treatment  algorithms to identify patients who are most likely to respond to treatment will be allowed by further information of the molecular basis for sensitivity or resistance to EGFR-targeted monoclonal antibodies. Individualized treatment for patients with metastatic colorectal cancer will be more realizable by the use of biomarkers like KRAS mutations for anti-EFGR monoclonal antibody treatment.

Interferon beta (IFNβ) is used in the treatment of multiple sclerosis (MS). It can reduce the relapse rate and the lesion formation of MRI and slow the progression of the disease. However, some patients develop neutralizing antibodies (NAbs) against interferon beta durin chronic administration of IFNβ. This has been observed in other protein-based drugs in long-term studies as well. Up to 25% of patients treated 3-times-weekly subcutaneously with IFNβ-1a develop Nabs. This could be observed for 2% of the once-weekly treated patients with IFNβ-1a intramuscular. The published data from clinical studies show that the efficacy in patients with NAb-positive compared with those who are NAb negative is reduced. Neutralizing antibodies can potentially cross the blood-brain barrier in IFN-beta-treated patients resulting in relapsing-remitting multiple sclerosis (RRMS) and affect the endogenous IFNβ function within the central nervous system (CNS).  This is confirmed by results of a study by Shapiro et al. It was demonstrated that high serum titers of NAbs (1865-19,320 tenfold reduction units ) in human astrocytes (in culture) inhibit toll-like receptor-3 ligand and endogenous IFNβ-mediated production of CXCL10 and IL-6. The case study shows that patients with positive titers of NAbs and BAbs in serum did not have detectable NAbs and BAbs that could be detected in the CSF. The absence of these antibodies in the cerebrospinal fluid does not eliminate in general that antibodies may cross the blood-brain barrier locally in the area of inflammation yet nor reach detectable levels in the CSF.

Display technologies have evolved from the outset and have now proved to be very useful when it comes to the task of selecting specific antibodies. Most of the selected antibodies via these platforms still need to be modified for their use in humans. At the same time they are restricted in their antigen recognition. These platforms are not well suited for in vivo selections. A novel cell-based antibody display platform is designed to help now. The validation of antibodies on the surface of T lymphocytes that can be used as part of a chimeric-immune receptor (CIR) mediating signaling ideal index the antigen-antibody interaction to show a demonstrable change in the T-cell phenotype. With this method an in vitro selection with a lentiviral-transduced human T-cell line worked successfully. A tumor-specific CIR on the surface of the cell was verified as an expression of carcino embryonic antigen. Based on effective interaction between the CIR and the tumor antigen, it was shown that the combination of CIR-mediated activation by FACS sorting of CD69 + T cells, it is possible to isolate the tumor by indication for a specific cell surface antigen. There was an accumulation of at least 103-fold after two passes, which led to a homogeneous population of T cells, which led to tumor-specific CIRS.