Characterization of second-generation monoclonal antibodies against carcinoembryonic antigen

Abstract

Background. A second‐generation panel of anti–carcinoembryonic antigen (CEA) monoclonal antibodies (MoAb) has been generated, and the specificity has been compared with that of the first panel of MoAb used to differentiate meconium antigen (MA) from CEA. Methods and Results. Four of the MoAb had similar specificities to the first‐generation panel of NP MoAb. MN‐15, like its first‐generation equivalent, NP‐1, reacts with normal cross‐reactive antigen (NCA), MA, and CEA; both MN‐15 and NP‐1 react strongly with granulocytes. MN‐2 has properties similar to Class II NP‐2, being reactive with MA and CEA, cross‐blocking binding to CEA by NP‐1, and having low reactivity with granulocytes; both NP‐2 and MN‐2 stain granulocytes in frozen tissue sections but show minimal staining of granulocytes in sections fixed in formaldehyde solution and embedded in Paraplast (Fischer Scientific, Pittsburgh, PA). MN‐14 demonstrates properties similar to the Class III anti‐CEA–specific MoAb, NP‐4, being unreactive with NCA and MA. MN‐14, as compared with NP‐4, demonstrated significantly superior tumor targeting in a human colon tumor xenograft model and consistently stronger staining of frozen sections of colon cancer. A fifth MoAb, MN‐3, had properties uniquely different from the NP series of MoAb, reacting strongly with granulocytes but not demonstrating the liquid‐phase ion‐sensitivity binding of CEA exhibited by MN‐15 and NP‐1. Conclusions. MN‐14 is being evaluated for radioimmunodetection of and radioimmunotherapy for CEA‐containing cancers, whereas MN‐3 is being studied for the radioimmunodetection of occult infections and sites of inflammation.

Carcinoembryonic antigen-immunoglobulin Fc fusion protein (CEA-Fc) for identification and activation of anti-CEA immunoglobulin-T-cell receptor-modified T cells, representative of a new class of Ig fusion proteins

“…MN-14 is a well-characterized medium-affinity mouse anti-human CEA antibody 22,24 that has been widely used for diagnosis and treatment of various CEA-expressing human cancers. 24,[24][25][26][27][28][29][30][31] We show here that MN-14 binds an epitope in region III (A3B3) of the CEA molecule, consistent with its designation as a Class III anti-CEAspecific monoclonal antibody.…”

“…21 Also, MN-14 was previously placed in the Primus class III, CEA-specific monoclonal antibodies that include some demonstrated to bind selectively in the A3B3 region. 22 Additional tests with an NC-A3 construct (J Shively, personal communication) further narrowed the MN-14 epitope to the A3 subregion.…”

Optimizing the use of combined radioimmunotherapy and hypoxic cytotoxin therapy as a function of tumor hypoxia

“…32,33 RS-7 anti-EGP-1 has been used for targeting and therapy of nonsmall cell lung cancers. 34,35 Both antibodies were radioiodinated by the chloramine-T method.…”

“…Invasive methods (e.g., O 2 microelectrodes, fluorescent Abs to hypoxic markers and cryospectrophotometry) as well as noninvasive methods (e.g., 32 P NMR spectral changes) have been used to study pO 2 changes after therapy. An initial rise in O 2 levels is found immediately after therapy.…”

Comparison of the monoclonal antibodies 17-1A and 323/A3: the influence of the affinity on tumour uptake and efficacy of radioimmunotherapy in human ovarian cancer xenografts

“…The effect of MAb affinity on the efficacy of radioimmunotherapy has been studied before, but the preference for low-or high-affinity MAbs was still elusive. In vivo, better tumour-targeting properties have been reported for a high affinity anti-CEA MAb (Hansen et al, 1993), but the MAb was equally effective in radioimmunotherapy when compared with a similar radiation dose of a low-affinity anti-CEA MAb (Blumenthal et al, 1992b). In this study no corrections were made for the immunoreactivity of the MAbs after radiolabelling.…”