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**anti-PSA IgE** is a novel mouse/human chimeric immunoglobulin E (IgE) antibody engineered with the variable regions from the murine IgG1 monoclonal antibody **AR47.47**, which specifically targets **prostate-specific antigen (PSA)**, a glycoprotein serine protease overexpressed in prostate cancer (PCa) due to structural changes in cancerous prostate tissue. It binds PSA, including free PSA and the prevalent PSA-α1-antichymotrypsin (ACT) complex found in PCa patient serum, as well as the AR47.47 epitope (amino acids 137–144). The antibody properly assembles (~190 kDa), is secreted from murine myeloma cells, and engages the high-affinity IgE receptor **FcεRI** on effector cells like mast cells and basophils. Unlike traditional IgG antibodies, it leverages IgE's potent effector functions to trigger immune activation: when complexed with PSA, it enhances antigen presentation by dendritic cells, induces CD4+ and CD8+ T-cell responses, and mediates anti-tumor protection in vivo, prolonging survival in human FcεRIα transgenic mice challenged with PSA-expressing tumors in prophylactic settings. Critically, it avoids systemic anaphylaxis as soluble mono-epitopic PSA forms fail to cross-link FcεRI, preventing degranulation, though artificial multi-epitopic antigens or anti-κ crosslinking do induce targeted inflammation.
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