NCI-V01-1646).

Only 10% of metastatic melanoma patients survive 5 years, even though many can achieve substantial tumor reduction by surgical resection and/or radiation therapy and/or systemic therapy. An effective, nontoxic, consolidation immunotherapy could benefit such patients. We initiated a randomized trial to compare 2 promising patient-specific immunotherapy cell products. Patients had to have a diagnosis of metastatic melanoma and availability of an autologous melanoma cell line. Patients were stratified by whether their most advanced stage had been regional or distant metastases, and by whether they had measurable disease at the time of treatment, then they were randomized to receive irradiated autologous proliferating tumor cells or autologous dendritic cells (DC) loaded with antigens from such cells. Both products were injected subcutaneously in 500 µg of granulocyte-macrophage colony stimulating factor, weekly for 3 weeks and then monthly for 5 months. Patients in the 2 arms did not differ in baseline characteristics. All patients received prescribed therapy. Treatment was well tolerated. At the time of initial analysis, with no patients lost to follow-up, 50% of patients deceased, and all surviving patients followed for at least 6 months after randomization, survival is superior in the DC arm (hazard ratio, 0.27; 95% confidence interval, 0.098-0.729) with median survival not reached versus 15.9 months, and 2-year survival rates of 72% versus 31% (P=0.007). This trial provides evidence that a DC vaccine is associated with longer survival compared with a tumor cell vaccine, and is consistent with previous data suggesting a survival benefit from this patient-specific immunotherapy.

Although AMP can induce an immediate IgE response in subjects allergic to betalactams and the structure of the side chain may contribute to the specificity of the response, our results indicate that in most instances crossreactivity with the other penicillins exists and that in the groups studied selective reactions to just AMP derived determinants were uncommon.

Background: IgE and IgG antibodies to penicillins can have different specificities. However, this response, including the recognition of the different parts of penicillin, has never been studied in the same subject. Objective: Study of the specificity of IgE and IgG antibodies and the relevant parts of the penicillin molecule that contribute to the hapten binding site in sera from human. Methods: Specific IgE antibodies were determined by RAST and specific IgG antibodies by ELISA. The recognition of the different molecules was studied by inhibition studies. Results: Seven sera with IgG and IgE antibodies to amoxicillin and benzyl penicillin were analyzed. IgE antibodies recognized mainly two different epitopes: in one, the side chain was a relevant part of the epitope, in the other, it was the nuclear portion. IgG antibodies recognized the nuclear portion in all instances. In the same subject, antibodies of different isotype and specificity were found. Conclusions: Subjects who develop simultaneously IgE and IgG antibodies to penicillins show different specificities. This proves that different populations of antibodies recognize different epitopes.

these results show that non-therapeutic exposure to penicillin can cause severe symptoms and that in vitro and in vivo testing can help in the diagnosis of such cases.