Monoclonal antibodies immune responses against

In addition to monoclonal antibody or chemotherapy, immunotherapy has been developed to target tumor antigen for the treatment of FL. The unique sequence of the protein, so-called idiotype (Id) protein, can be a target of immunotherapy. Because Id protein can induce humoral and cellular immune responses against idiotype protein, vaccination with Id protein can decrease the risk of progression. However, the mechanism of anti-Id response has been unclear. 

Chatenoud L, Baudrihaye MF, Chkoff N. Restriction of the human in vivo immune response against the mouse monoclonal antibody OKT3. J Immunol 1986 137 830-838. 

Immune responses also may be mounted against therapeutic monoclonal antibodies. The class of monoclonal antibody as well as the animal species from which the distinguishing amino acid sequences of antibody are derived strongly influence immunogenicity. Suffice to say that mouse antibodies, monoclonal or poly-... 

Clinical pharmacology Basiliximab is a chimeric (mouse/human) interleukin-2 receptor antagonist. It is directed against the interleukin-2 receptor-alpha chain (CD25) on activated T-lymphocytes, and is a potent inhibitor of interleukin-2-mediated activation of lymphocytes, a critical pathway in the cellular immune response involved in allograft rejection. Another anti-CD25 monoclonal antibody, dacUzumab (Zenapax), has the same indication as basiliximab. 

The monoclonal antibodies used as immunosuppressive agents in tissue transplantation include muromonoab-CD3, daclizumab and basiliximab. Muromonoab-CD3 binds to a specific site on CD3 receptors and interferes with the ability of the TCR to bind the antigen and also inhibits CD3 receptor-dependent signal transduction mechanisms, all of which result in immune suppression. Both daclizumab and basiliximab are monoclonal antibodies directed against IL-2 receptors and consequently inhibit IL-2-dependent responses after tissue transplantation, resulting in immune suppression. The monoclonal antibodies used as immunosuppressive agents are described in detail in Chapter 5. 

Bispecific monoclonal antibodies are artificially developed antibodies with antigenbinding sites physically linked to different specificities. It is thought that bispecific monoclonal antibodies activate the cellular immune response by crosslinking immune cells to tumor cells, thus circumventing the proper structures for tumor cell-immune cell interactions (Koelemij et al., 1999). These antibodies are effective in low concentrations in vivo. For example, Kufer et al. (1996) have combined the anti-CD3 specificity directed against T cells in a bispecific monoclonal antibody, with the specificity against the tumor-associated 17-1A antigen. This antibody could be a major improvement, for example, in the therapy for disseminated micrometastatic tumor cells. 

To improve the specific response against microcystin immimoconjugates, synthetic lipopeptides were used as adjuvants and were found to invoke a greater immune response than the use of classical adjuvants such as Freunds adjuvant. However, an ELISA for the detection of free microcystin was not developed using these antibodies. Cross-reactivities of various microcystin variants and nodn-larin with monoclonal antibodies have been found affecting to the specificity of these antibodies for the recognition of the mentioned toxins. The number of purified microcystin variants that have been tested by ELISA using monoclonal antibodies shows marked differences between methods. 

---