Homophilic peptide inhibits growth of malignant murine and human B cells.

A homophilic peptide from the T15 plasmacytoma inhibits growth of murine and human B cell tumors. This finding confirms the hypothesis that B cell malignancies are driven by a self-binding epitope in the B cell receoptor (BCR) proposed as the pathogenesis of chronic lymphocytic leukemia (CLL).

Physical and biological properties of homophilic therapeutic antibodies.

Homophilic antibodies have been discovered in mice and primates and can also be engineered. Compared to conventional antibodies, homophilic antibodies form lattices on targets leading to enhanced binding via polyvalent attachment. Previously, we have observed a paradoxical dose/potency effect with an engineered homophilic antibody against a human lung cancer tumor.

Paradoxical concentration effect of a homodimerizing antibody against a human non-small cell lung cancer cell line.

Drug dosing is commonly based on the dogma that, increasing the dose maximizes the therapeutic response until a dose level that is prohibitively toxic is reached. This doctrine also applies to antibody therapy, as several protocols have explored dose escalation. We have analyzed the effect of different amounts of a homophilic Herceptin targeting a human lung tumor cell line, and discovered that the normal dose-potency relationship does not apply.