The data presented in this report demonstrate that young foals are capable of immune activation following a 3-dose series with a multivalent vaccine, despite presence of maternal antibodies. Although immune activation does not automatically confer protection, several of the immune indicators measured showed comparable expression in foals vaccinated at 3 months relative to control foals vaccinated at age 6 months. In high-risk situations where immunity may be required earlier than following a conventional vaccine series, our data provide evidence that foals respond to immunisation initiated at 3 months in a comparable manner to foals initiated at an older age.

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. Here, we have investigated some biophysical properties of homophilic antibodies and also studied the inhibition of human tumor growth in a xenograft model using homophilic Herceptin. Dimerization and viscosity of two homophilic antibodies are greater at physiological temperature than at 4°C. Similarly, binding to solid-phase antigen is greater at 37°C than at room temperature or 4°C. Dimer formation is higher at therapeutic concentration, supporting the notion that preformed dimers in solution are the effective molecular species responsible for polyvalent target binding and enhanced therapeutic potency.

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. To study this paradoxical effect of antibody concentration on potency, we examined the molecular species of the homophilic Herceptin under different concentrations using size exclusion chromatography and gel electrophoresis. We also varied experimental conditions in FACS tumor targeting, such as concentration of antibody, membrane immobilization, temperature, and antibody homo/dimer immobilization. We observed that high concentrations of homophilic Herceptin reduce targeting, and also noted the tumor growth arrest in the xenograft mice after the tumor reached a critical size. The therapeutic window appears to be defined by tumor size and antibody concentration. Since the concentration of this homophilic antibody defines the optimum targeting window, our data suggest the therapeutic dose of antibody should be matched with the tumor burden.

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).